Structural and oxidative stabilization of spray dried fish oil microencapsulates with gum arabic and sage polyphenols: Characterization and release kinetics.

✅ 全文

阿拉伯鼠李丹宁和鼠尾草多酚对喷雾干燥鱼油微胶囊的结构与氧化稳定性:表征及释放动力学研究

作者 Binsi P K; Nayak Natasha; Sarkar P C; Jeyakumari A; Muhamed Ashraf P; Ninan George; Ravishankar C N 期刊 Food chemistry 发表日期 2017 卷/期/页码 Vol. 219 ISSN 1873-7072 DOI 10.1016/j.foodchem.2016.09.126 类型 原创研究 (Original Research)

📄 中文摘要 Chinese Abstract

中文
Omega-3脂肪酸如EPA和DHA具有显著的健康益处,包括抗炎和心脏保护作用。然而,它们的高氧化敏感性限制了其在食品(尤其是婴幼儿配方奶粉)中的直接添加。喷雾干燥微胶囊化是一种经济有效的方法,可保护鱼油免受氧化降解并提高生物利用度。尽管具有优势,喷雾干燥由于高温和机械剪切力可能导致乳液不稳定、胶囊塌陷或氧化。天然交联剂如植物多酚——特别是来自鼠尾草(Salvia officinalis)的多酚——是合成交联剂的有前景的替代品,可通过蛋白质-多酚相互作用提供结构稳定性和抗氧化保护。阿拉伯胶作为常见的壁材可补充这些体系,但在苛刻干燥条件下单独使用时结构强度不足。

📋 英文结构化总结 English Structured Summary

全文整理

EN

Background:

Omega-3 fatty acids such as EPA and DHA offer significant health benefits, including anti-inflammatory and cardioprotective effects. However, their high susceptibility to oxidation limits direct incorporation into foods, especially infant formulas. Microencapsulation via spray drying is a cost-effective method to protect fish oil from oxidative deterioration and improve bioavailability. Despite its advantages, spray drying poses challenges due to high temperatures and mechanical shear, which can destabilize emulsions and promote capsule collapse or oxidation. Natural cross-linking agents like plant polyphenols—particularly from sage (Salvia officinalis)—are promising alternatives to synthetic cross-linkers, offering both structural stabilization through protein-polyphenol interactions and antioxidant protection. Gum arabic, a common wall material, complements these systems but lacks sufficient structural robustness alone under harsh drying conditions.

Methods:

Emulsions were prepared using sodium caseinate (wall polymer), gum arabic (co-polymer), and fish oil, with or without 1% (w/w) sage extract. Emulsions were homogenized at 25,000 rpm and spray-dried at 160°C inlet and 80°C outlet temperatures. Encapsulation efficiency (EE) was determined gravimetrically by measuring surface and total oil content. Morphology was analyzed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Oxidative stability was assessed via accelerated storage at 60°C for 7 days, monitoring peroxide value (PV) and thiobarbituric acid reactive substances (TBARS). In vitro release was tested in buffered saline (pH 7.4, 60% phosphate buffer/40% ethanol) and simulated gastrointestinal fluids (SGF with pepsin, SIF with pancreatin). Statistical analysis was performed using one-way ANOVA (p < 0.05).

Results:

The SOE (fish oil + sage extract) emulsion exhibited superior stability (98.67% unseparated phase after 24 h vs. 96.66% for FOE) and smaller, more uniform droplets (<2 µm vs. 3–10 µm). SEM and AFM revealed that SOE microcapsules had smoother surfaces, better sphericity, and fewer collapses compared to FOE. Encapsulation efficiency was significantly higher for SOE (73.27%) than FOE (68.96%), with lower surface oil (3.4 vs. 3.87 g/100 g powder). FTIR analysis confirmed polyphenol-mediated cross-linking in SOE, evidenced by shifts in amide I/II bands and appearance of an ester peak at 1744 cm⁻¹. During accelerated storage, SOE showed slower increases in PV and TBARS, indicating enhanced oxidative stability. In vitro release in buffered saline was markedly lower for SOE (cumulative 19.74% over 4 h) versus FOE (55.22%). In simulated GI fluids, SOE released less oil in gastric phase (64.26% vs. 71.71%) and comparable amounts in intestinal phase (~15%), suggesting controlled release.

Data Summary:

Encapsulation efficiency: SOE = 73.27%, FOE = 68.96%. Surface oil: SOE = 3.4 g/100 g, FOE = 3.87 g/100 g. Moisture content: SOE = 5.01%, FOE = 5.91%. Bulk density: SOE = 0.42 g/mL, FOE = 0.39 g/mL. After 7 days at 60°C, PV and TBARS values were significantly lower in SOE than FOE. Cumulative oil release in buffered saline after 4 h: SOE = 19.74%, FOE = 55.22%. Oil release in SGF: SOE = 64.26%, FOE = 71.71%; in SIF: ~15% for both.

Conclusions:

The combination of gum arabic and sage polyphenols synergistically enhances the structural integrity and oxidative stability of spray-dried fish oil microcapsules. Sage polyphenols act as natural cross-linkers, forming a robust polymer network that resists thermal and mechanical stress during drying, reduces surface oil, and slows lipid oxidation during storage. The resulting microcapsules exhibit controlled release behavior, with minimal leakage in aqueous environments and targeted release in gastrointestinal conditions. This approach offers a safe, natural, and effective strategy for delivering omega-3 fatty acids in functional foods.

Practical Significance:

This technology enables the development of stable, oxidatively protected fish oil ingredients suitable for incorporation into infant formulas, dairy products, and other functional foods without compromising sensory or nutritional quality. The use of Generally Recognized as Safe (GRAS) materials like sage extract and gum arabic supports clean-label trends and avoids synthetic additives, meeting consumer demand for natural, health-promoting food products.

📋 中文结构化总结 Chinese Structured Summary

中文

背景:

Omega-3脂肪酸如EPA和DHA具有显著的健康益处,包括抗炎和心脏保护作用。然而,它们的高氧化敏感性限制了其在食品(尤其是婴幼儿配方奶粉)中的直接添加。喷雾干燥微胶囊化是一种经济有效的方法,可保护鱼油免受氧化降解并提高生物利用度。尽管具有优势,喷雾干燥由于高温和机械剪切力可能导致乳液不稳定、胶囊塌陷或氧化。天然交联剂如植物多酚——特别是来自鼠尾草(Salvia officinalis)的多酚——是合成交联剂的有前景的替代品,可通过蛋白质-多酚相互作用提供结构稳定性和抗氧化保护。阿拉伯胶作为常见的壁材可补充这些体系,但在苛刻干燥条件下单独使用时结构强度不足。

方法:

乳液由酪蛋白酸钠(壁聚合物)、阿拉伯胶(共聚合物)和鱼油制备,添加或不添加1%(w/w)鼠尾草提取物。乳液在25,000 rpm下均质化,并在160°C入口温度和80°C出口温度下喷雾干燥。包封效率(EE)通过测量表面油和总油含量以重量法测定。形态学分析采用扫描电子显微镜(SEM)和原子力显微镜(AFM)。氧化稳定性通过60°C加速储存7天进行评估,监测过氧化值(PV)和硫代巴比妥酸反应物质(TBARS)。体外释放试验在缓冲盐水(pH 7.4,60%磷酸盐缓冲液/40%乙醇)和模拟胃肠液(含胃蛋白酶的SGF、含胰酶的SIF)中进行。统计分析采用单因素方差分析(p < 0.05)。

结果:

SOE(鱼油+鼠尾草提取物)乳液表现出更优的稳定性(24小时后未分离相为98.67%,而FOE为96.66%),且液滴更小、更均匀(<2 µm对比3–10 µm)。SEM和AFM显示SOE微胶囊表面更光滑、球形度更好、塌陷更少。SOE的包封效率(73.27%)显著高于FOE(68.96%),表面油含量更低(3.4对比3.87 g/100 g粉末)。FTIR分析证实了SOE中多酚介导的交联作用,表现为酰胺I/II带位移和1744 cm⁻¹处酯键峰的出现。加速储存期间,SOE的PV和TBARS增长较慢,表明氧化稳定性增强。缓冲盐水中SOE的体外释放显著低于FOE(4小时累积释放19.74%对比55.22%)。在模拟胃肠液中,SOE在胃相释放较少油脂(64.26%对比71.71%),在肠相释放量相当(约15%),表明具有控释特性。

数据总结:

包封效率:SOE = 73.27%,FOE = 68.96%。表面油:SOE = 3.4 g/100 g,FOE = 3.87 g/100 g。水分含量:SOE = 5.01%,FOE = 5.91%。堆积密度:SOE = 0.42 g/mL,FOE = 0.39 g/mL。60°C储存7天后,SOE的PV和TBARS值显著低于FOE。缓冲盐水中4小时累积油释放:SOE = 19.74%,FOE = 55.22%。SGF中油释放:SOE = 64.26%,FOE = 71.71%;SIF中两者均约为15%。

结论:

阿拉伯胶与鼠尾草多酚的协同作用显著增强了喷雾干燥鱼油微胶囊的结构完整性和氧化稳定性。鼠尾草多酚作为天然交联剂,形成坚固的聚合物网络,抵抗干燥过程中的热应力和机械应力,减少表面油,并减缓储存期间的脂质氧化。所得微胶囊表现出控释行为,在水性环境中渗漏最小,在胃肠道条件下实现靶向释放。该方法为功能性食品中omega-3脂肪酸的递送提供了一种安全、天然且有效的策略。

实际意义:

该技术能够开发稳定的、抗氧化保护的鱼油原料,适用于婴幼儿配方奶粉、乳制品及其他功能性食品的添加,且不影响感官或营养品质。使用鼠尾草提取物和阿拉伯胶等一般认为安全(GRAS)的材料支持清洁标签趋势,避免合成添加剂,满足消费者对天然、促进健康食品产品的需求。

📖 英文全文 English Full Text

EN

Accepted Manuscript Structural and oxidative stabilization of spray dried fish oil microencapsulates with gum arabic and sage polyphenols: characterization and release kinetics

P.K. Binsi, Natasha Nayak, P.C. Sarkar, A. Jeyakumari, P. Muhamed Ashraf,

George Ninan, C.N. Ravishankar PII:

S0308-8146(16)31521-7 DOI: http://dx.doi.org/10.1016/j.foodchem.2016.09.126

Reference:

FOCH 19906 To appear in:

Food Chemistry Received Date:

18 April 2016 Revised Date:

13 August 2016 Accepted Date:

19 September 2016 Please cite this article as: Binsi, P.K., Nayak, N., Sarkar, P.C., Jeyakumari, A., Muhamed Ashraf, P., Ninan, G.,

Ravishankar, C.N., Structural and oxidative stabilization of spray dried fish oil microencapsulates with gum arabic and sage polyphenols: characterization and release kinetics, Food Chemistry (2016), doi: http://dx.doi.org/10.1016/ j.foodchem.2016.09.126

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

1

Structural and oxidative stabilization of spray dried fish oil microencapsulates

1 with gum arabic and sage polyphenols: characterization and release kinetics

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3 Binsi PK1*, Natasha Nayak1, Sarkar PC2., Jeyakumari A3, Muhamed Ashraf P1.,George

4 Ninan1, Ravishankar CN1 5

6 1. ICAR- Central Institute of Fisheries Technology (CIFT), Matsyapuri, Willington Island,

7 Cochin, India – 682 029 8 2. ICAR - Indian Institute of Natural Resins and gums, Namkum, Ranchi-834 010

9 3. ICAR-Mumbai Research Centre of CIFT, Sector-1, Vashi, Navi Mumbai- Maharashtra

10 400 703 11

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14 * Corresponding author 15 Tele: ++ 91-484 - 2412300

16 Fax: ++ 91 - 484 – 2668212 17 E-mail: binsipk@yahoo.com

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19 Stable fish oil-sage extract microencapsulates ..

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Abstract 21 The synergistic efficacy of gum arabic and sage polyphenols in stabilising capsule wall

22 and protecting fish oil encapsulates from heat induced disruption and oxidative deterioration

23 during spray drying was assessed. The emulsions prepared with sodium caseinate as wall

24 polymer, gum arabic as wall co-polymer and sage extract as wall stabiliser was spray dried using

25 a single fluid nozzle. Fish oil encapsulates stabilised with gum arabic and sage extract (SOE)

26 exhibited significantly higher encapsulation efficiency compared to encapsulates containing gum

27 arabic alone (FOE). Scanning electron microscopic and atomic force microscopic images

28 revealed uniform encapsulates with good sphericity and smooth surface for SOE, compared to

29 FOE powder. In vitro oil release of microencapsulates indicated negligible oil release in buffered

30 saline whereas more than 80% of the oil loaded in encapsulates were released in simulated GI

31 fluids. The encapsulates containing sage extract showed a lower rate of lipid oxidation during

32 storage.

33 Key words: Fish oil encapsulates, oxidation, sage extract, polyphenol

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Introduction 43 The health benefits conferred by Omega-3 fatty acids, such as eicosapentaenoic acid

44 (EPA) and docosahexaenoic acid (DHA), arise mainly from its anti-inflammatory and anti- 45 arrhythmic properties that are beneficial to cardiac functioning (Endo, & Arita, 2016). The

46 epidemiological studies have suggested that high fish consumption is inversely associated with

47 cognitive impairment, depression and development of dementia or Alzheimer’s disease (Freund- 48

Levi et al., 2014). In spite of all these health benefits, there are certain human food safety

49 concerns associated with dietary intake of omega-3 rich fish oil. Omega-3 fatty acids are highly

50 susceptible to oxidative changes, producing toxic secondary and tertiary compounds. This inturn

51 restricts the amount of fish oil that can be directly consumed or added to the foods, particularly

52 in infant formula.

53 Microencapsulation of fish oil in a stable wall matrix has been recognised as a suitable

54 technique for the delivery of fish oil supplements, as it reduces oxidative deterioration and

55 improves bioavailability. Among the various techniques used for fish oil microencapsulation, the

56 cheapest one is spray-drying and its cost is 30-50 times lesser than freeze-drying (Gharsallaoui,

57 Roudaut, Chambin, Voilley, & Saurel, 2007). However, the high operational temperature

58 coupled with the mechanical shearing during atomisation is a major challenge in the

59 encapsulation process, as these forces may destabilise the emulsion, and promote capsule

60 collapse as well as oxidation of fish oil during the drying process. Consequently, use of cross- 61 linking agents very often becomes necessary as the ionic nature of the interactions between the

62 wall forming materials alone does not guarantee the structural integrity of the resulting

63 microcapsules (Koupantsis, Pavlidou, & Paraskevopoulou, 2016). Presently, formaldehyde,

64 glutaraldehyde as well as the enzyme transglutaminase have been employed as protein cross- 65

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linking agents. However, owing to the adverse health and environmental effects associated with

66 aldehydes, and the low economic viability of enzyme mediated processes, the demand for natural

67 and economically sustainable alternatives is high. Hence, incorporation of natural cross-linkers

68 and antioxidants in the emulsion may be highly advisable, especially when spray drying is

69 involved.

70 Controlled release of food ingredients at the right place and right time is another key

71 functionality that can be provided by microencapsulation. Generally, carbohydrate and protein- 72 based microcapsules are water soluble and hence not suitable for controlled-release applications

73 (Cho, Shim, & Park, 2003). However, if the proteins are cross-linked into stable forms, the

74 application of proteins as wall material would be greatly increased for targeted and controlled

75 delivery of sensitive supplements. Cross-linking changes the net charge of protein molecules,

76 and hence can be explored to alter the solubility pattern of protein in a given medium. This has

77 the added technical advantage that the microcapsules act as supplement for omega-3 fish oil and

78 protein, simultaneously.

79 Plant essential oils rich in polyphenols are multifunctional and are ideal for encapsulating

80 fish oil, as they are effective protein cross-linkers, and at the same time serve as potent

81 antioxidant for fish oil by acting as reducing agents or singlet oxygen scavengers. Polyphenols

82 are known to react under oxidising conditions with side chain amino groups of peptides, leading

83 to the formation of protein cross-links, as shown in gelatin–pectin microparticles which

84 possessed enhanced lipophilicity and resistance to thermal degradation after cross-linking with

85 polyphenols in coffee and grape juice (Strauss, & Gibson, 2004). Similarly, significant cross- 86 linking ability of tannic acid on myofibrillar protein was reported (Prodpran, Benjakul, &

87 Phatcharat, 2012). Plant polyphenolic compounds show strong interaction with milk proteins,

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such as casein, as well. Previously, strengthening of the microcapsule walls through reticulation

89 with the use of glycerol and tannic acid for sodium caseinate or whey protein isolate- 90 carboxymethylcellulose microcapsules was reported (Koupantsis et al., 2016). The interaction

91 between proteins and plant phenols proceeds with polymerization mainly by the formation of

92 non-covalent interactions bridged through numerous hydrogen bonds (Frazier et al., 2010) as

93 well as through covalent C–N or C–S bonds (Strauss, & Gibson, 2004). Herbs, such as sage

94 (Salvia sp.), are included under ‘spices and other natural seasonings and flavourings’ that are

95 generally recognized as safe, by USFDA. The antioxidant activity of sage is mainly related to

96 two phenolic diterpenes, carnosic acid and carnosol, which are effective free-radical scavengers

97 (Dorman, Peltoketo, Hiltunen, & Tikkanen, 2003). Gum arabic is a commonly employed agent

98 for encapsulating fish oil and other vegetable oils, because of its colloidal functionality and

99 compatibility with most carbohydrates and proteins that are commonly employed as wall

100 polymers. Nevertheless, the efficacy of herbal extracts on structural stabilisation of fish oil

101 encapsulate is not evaluated so far. Hence, the objective of the present study was to evaluate the

102 efficacy of sage extract and gum arabic on structural and oxidative stabilisation of fish oil

103 encapsulates with an emphasise on minimising the adverse effect of elevated temperature and

104 mechanical shearing during spray drying. Apart from that, the oxidative stability of the

105 encapsulates during accelerated oxidative atmosphere and oil release pattern in buffered saline

106 and gastrointestinal environment was evaluated.

107 2. Materials and methods 108 2.1. Raw materials

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Gum arabic from Acacia Senegal with an average molecular weight of 285 kDa (containing <1%

110 protein and < 1% insoluble matter), pepsin (activity of 800–2500 ml units/mg of protein) and

111 pancreatin 4NF, both of porcine origin, were procured from Hi-Media Pvt Ltd. (Mumbai, India).

112 Sodium caseinate of extrapure grade was purchased from Sisko Research Laboratories Pvt. Ltd.

113 (Mumbai, India). Fish oil extracted from Indian oil sardine (Sardinella longiceps) with known

114 fatty acid composition was used for microencapsulate preparation (Myristic acid: 11.98%, stearic

115 acid: 4.88%, palmitic acid: 23.66%, palmitoleic acid:13.22, oleic acid:8.55%, EPA:13.55%,

116 DHA:10.42%). Sage (Salvia officinalis) extract containing 45% (w/w) essential oil was

117 purchased from Synthite Industries Ltd. (Cochin, India). The composition of sage extract as

118 determined by Gas Chromatography-Mass Spectroscopic (GC-MS-MS) analysis indicated the

119 following components. 1,8, Cineole (12.8%), α-humulene (11.8%), viridiflorol (11.1%), β- 120 caryophyllene (5.8%), α-thujone (4.2%), β-thujone (4.1%), carvacrol (3.6%), thymol (3.4%), β- 121 pinene (3.3%), α-pinene (3.1%) , camphor (3.1%), limonene (2.8%), borneol (2.5%), linalool

122 (2.1%), viridiflorene (2.1%), Myrcene (1.9%), p-cymene (1.2%), linalylacetate (1.1%),

123 camphene (0.9%), 14-hydroxy-9-epi- (E) –caryophyllene (0.8%), caryophyllene oxide (0.7%), γ- 124 muurolene (0.7%),δ -cadinene (0.6%), Aromadendrene (0.4%).

125 2.2. Preparation of emulsions 126 The composition of the emulsions for spray drying was established based on our previously

127 reported results (Jeyakumari, Janarthanan, Chouksey, & Venkateshwarlu, 2014). The stability of

128 the emulsions were confirmed by quantifying phase separation over 24h and microscopic

129 examination of emulsion droplets. Accordingly, emulsions with 7.5% total solids was prepared

130 with sodium caseinate, gum arabic and fish oil in the ratio of 2:2:1 (ie. 3g sodium caseinate, 3g

131 gum arabic and 1.5g fish oil for 100 ml of emulsion). Two different emulsion formulations for

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encapsulation were prepared namely, fish oil (FO emulsion) and fish oil containing 1% sage

133 extract (w/w of fish oil) keeping the total solid content constant at a level of 7.5% (SO

134 emulsion). Emulsions were prepared by dissolving sodium caseinate in a water bath held at 40ºC

135 with intermittent stirring. After proper dissolution, the solution was allowed to cool and gum

136 arabic was added with continuous stirring to avoid lump formation. After the dissolution of wall

137 material, fish oil previously mixed with 1% sage extract was added to the solution. The mixture

138 was homogenized with a high speed homogenizer (Poly system PT 2100, Kinematica, AG) at

139 25000rpm for 5 min. Prior to spray drying, the emulsions were allowed to stabilize at 4ºC for 1 h.

140 2.3. Spray drying of emulsions 141 Spray drying was employed using a pilot-scale spray dryer (Hemraj Pvt Ltd, Mumbai, India)

142 with an atomizer nozzle of 0.5 mm diameter at 450 KPa. The inlet and outlet air temperatures

143 were maintained at 160˚C and 80˚C, respectively and feed rate was adjusted to 15-22 g/min. The

144 encapsulate powder prepared from FO emulsion, SO emulsion are hereafter designated as FOE

145 and SOE, respectively. Three independent trials of encapsulations were carried out for both the

146 emulsions.

147 2.4. Characterization of emulsion 148 2.4.1. Emulsion stability index (ESI)

149 About 150 ml aliquots of each sample were transferred to graduated cylinders of 250 ml and kept

150 at 4oC for 24 h. The volume of the bulk unseparated phase was measured after 24 h and the

151 stability was expressed in terms of stability index:

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Where: H0 represents the emulsion initial volume and H1 is the unseparated phase volume.

154 2.4.2. Emulsion microstructure 155 The microstructure of the emulsion was analysed by smearing the emulsion sample onto a

156 microscope slide and observing under an inverted microscope (Leica Microsystems, Wetzlar,

157 Germany) and an atomic force microscope (XE-100, Park Systems, Korea) in non-contact mode

158 employing silicon tips. Emulsions were prepared freshly and analysed at room temperature

159 (25ºC). For inverted microscopy, the images were obtained at 200x magnification and the

160 average size of 5 droplets each of predominant dimensions was determined using image

161 processing software (Leica Microsystems Imaging Solutions, Cambridge, UK) with a CCD

162 camera. For AFM analysis, 10 µl of the emulsion sample was directly pipetted over silica wafers,

163 air dried and analysed over 4µ scanning area.

164 2.5. Analysis of microencapsulates 165 2.5.1. Fourier transform-infrared spectroscopic analysis (FTIR)

166 The FTIR analysis of both the encapsulates were carried out immediately after spray drying

167 using a Thermo Fisher Scientific FT-IR spectrometer (Model NicoletTM iSTM 10, Thermo Fisher

168 Scientific, Waltham, MA), by KBr pellet method in the wavelength range of 4000-400 cm-1. The

169 spectra was analysed using OMNIC software (Thermo Fisher Scientific).

170 2.5.2. Determination of encapsulation efficiency and percentage loss (EE) of oil

171 Surface oil from the spray dried powder was extracted by pentane according to the method

172 described elsewhere (Dieffenbacher & Lüthi, 1986) with slight modifications. 1 g of powder was

173 mixed with 10 ml pentane in a 100 ml Erlenmeyer flask with a stopper. The mixture was shaken

174 for 2.5 h at 25ºC and then passed through a Whatmann No. 4 filter paper. Solvent collected was

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evaporated and surface oil present was determined gravimetrically. The total oil was extracted

176 from the original powder, whereas encapsulated oil was extracted from the residual dried powder

177 after extracting the free oil. About 0.5g of original powder and residual dried powder,

178 respectively, was mixed with aqueous hydrochloric acid solution (2 M, 4 ml) and boiled at 95ºC

179 for 30 min. After cooling, ethanol (2 ml) was added to the mixture and shaken vigorously. To

180 this, 10 ml of petroleum ether was added and the mixture was centrifuged at 9000 rpm for 5 min

181 at 25 ºC. The upper phase was transferred dried in an oven at 105ºC and the oil present in the

182 sample was determined gravimetrically.

183 Encapsulation efficiency (EE %) was determined by the following formula as described by

184 Wang, Liu, Chen, & Selomulya (2016) 185

186 Where, TO is the total oil per gram of encapsulate powder on dry weight basis, SO is the surface

187 oil per gram of encapsulate powder on dry weight basis.

188 Percentage loss during spray drying was calculated based on the total oil content of encapsulates

189 and loaded oil per gram of wall polymer in the emulsion on dry weigh basis.

190

191 Where, LO is the total oil loaded per total solid content in the emulsion (total weight of sodium

192 caseinate, gum arabic and oil), ie, here LO = 0.20 g oil/g solid weight.

193 2.5.3 Morphology of microencapsulates.

194 2.5.3.1 Scanning electron microscopy (SEM) 195

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The surface appearance and morphology of FOE and SOE microencapsulates were examined by

196 SEM (XL 30 Philips, Netherlands). Samples were fixed onto double-sided adhesive carbon tabs

197 mounted on SEM stubs, coated with gold in a sputter coater, and examined by SEM.

198 2.5.3.2. Atomic force microscopy (AFM) 199 The morphology of the FOE and SOE microencapsulates was investigated by atomic force

200 microscope in non-contact mode employing silicon tips, in the similar way the emulsion droplet

201 was analysed. The samples (100 mg) were dispersed in distilled water (10 ml) by sonicating with

202 a probe sonicator. A 10 µl of the dispersed sample was pipetted over silica wafers, air dried and

203 analysed for its surface characteristics.

204 2.5.4. Physical properties of microencapsulates

205 2.5.4.1. Determination of moisture content 206

Moisture content of microencapsulates was determined by AOAC method (AOAC, 2000).

207 2.5.4.2. Determination of bulk density 208 Briefly, 2g powder was loosely packed in 10 ml graduated cylinder and the volume was

209 recorded. Bulk density of the powder was calculated by dividing weight of the sample by its

210 volume.

211 2.5.4.3. Hygroscopicity 212 One gram of sample was placed in a desiccator with a saturated solution of NaCl (relative

213 humidity of 75.3%). After one week, samples were weighed and hygroscopicity was expressed

214 as the amount of absorbed moisture per 100 g of sample (g/100 g).

215

11

2.5.5. Oil release properties of microencapsulates

216 2.5.5.1. Release characteristics of encapsulates in buffered saline

217 The release kinetics of microencapsulates in buffered saline was analysed by the method given

218 by Hosseini, Zandi, Rezaei, & Farahmandghavi (2013). Microencapsulates (20 mg) were placed

219 in a centrifuge tube containing 5 ml of 60% phosphate buffer saline (pH 7.4) and 40% ethanol.

220 The mixture was incubated at ambient temperature (27±2 ºC) under gentle agitation. At specific

221 time interval of 1h, samples were centrifuged at 9000 rpm for 5 min at 25 ºC. A specific volume

222 of supernatant was sucked out for analysis, and was replaced with an equivalent volume of fresh

223 media. The cumulative amount of oil released in the medium at various sampling time intervals

224 was determined from the standard curve derived separately for fish oil at 215 nm (derived from

225 the absorbance spectra obtained for the fish oil) and fish oil containing 1% sage extract at 275

226 nm (derived from the absorbance spectra obtained for fish oil containing 1% sage extract), using

227 a UV–VIS spectrophotometer. Cumulative percentage of fish oil released was obtained by

228 dividing the cumulative amount of oil released at each sampling time point (Mt) to the total

229 weight of the oil present in the encapsulates (Mo)

230

231 2.5.5.2. Oil release kinetics during in vitro digestion using simulated GI fluids

232 Simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing

233 pancreatin were prepared according to the methods given in the US Pharmacopeia (2000). In the

234 case of SIF, a 10-fold higher concentration of pancreatin was used since the sample used was dry

235

12

powder, as suggested previously by Kosaraju, D'ath, & Lawrence (2006) for encapsulated fish

236 oil. Microcapsules (5.0 g) were initially subjected to gastric digestion at 37oC at 100rpm for 2 h.

237 Further, SIF was added and intestinal digestion was continued under similar conditions for

238 another 3h. The quantity of oil released from the microcapsules after exposure to SGF and SIF

239 was determined separately by the method given by Patten, Augustin, Sanguansri, Head, &

240 Abeywardena (2009). Microstructure of the encapsulates was monitored prior and after gastric

241 and intestinal digestion separately using an inverted microscope (Leica Microsystems, Wetzlar,

242 Germany) by directly mounting the emulsion sample at ambient temperature (25 ºC) at 200x

243 magnification.

244 2.5.6. Measurement of lipid oxidation in microencapsulates by accelerated storage study

245 2.5.6.1. Determination of lipid oxidation products

246 The oxidative stability of the microcapsules was evaluated by accelerated storage at 60ºC for 7

247 days, using a hot air oven. The microencapsulates (about 30 g) was placed in sealed glass bottles

248 and covered with aluminum foil to avoid exposure to light. A 30 g sample of pure fish oil used

249 for the encapsulation (PFO) was also analyzed to compare the result. The peroxide values (PV)

250 of microencapsulates were determined during definite intervals according to the method

251 described by Shantha and Decker (1994). Hydroperoxide concentration in the sample was

252 determined using a standard curve made from cumene hydroperoxide and expressed as mEq

253 O2/kg of oil loaded. Changes in secondary oxidation products of the emulsion were determined

254 by measuring Thiobarbituric acid reactive substances (TBARS) according to the method

255 described by McDonald and Hultin (1987) and expressed as mg of malonaldehyde / kg powder.

256 2.5.6.2. Colour 257

13

The colour of microencapsulates were determined by Hunter lab color meter (Color Flex, Hunter

258 Lab Inc., Reston, VA, USA). The samples were filled in a 64 mm glass sample cup to a pre- 259 determined level and L*, a* and b* parameters were determined.

260 2.5.7. Statistical analysis 261 The data obtained were analyzed by one way analysis of variance (ANOVA) using SPSS

262 software version 16.0 (SPSS Inc, Chicago, Illinois, USA). All mean separations were carried out

263 at significance level of 95% (p<0.05).

264 3. Results and discussion 265 3.1. Characterization of emulsion

266 3.1.1. Emulsion stability index 267 Obtaining a stable liquid emulsion is a prerequisite for proper encapsulation in spray-dried

268 powders. Our previous studies indicated that sodium caseinate along with the surface active gum

269 arabic formed stable emulsions with fish oil, without any visible phase separation (Jeyakumari et

270 al., 2014). In the present study, the stability of emulsions prepared with and without sage extract

271 for a period of 24 h was confirmed prior to spray drying. The results indicated that both the

272 emulsions were kinetically stable, with an unseparated phase fraction of 96.66% and 98.67%,

273 respectively, for FO and SO emulsions (Table 1). Several studies have inferred that properties

274 and stability of fish oil emulsions are much affected by the level of minor ingredients, especially

275 emulsifier (Jiménez-Martín, Gharsallaoui, Pérez-Palacios, Carrascal, & Rojas, 2015; Komaiko,

276 Sastrosubroto, & McClements, 2016). It appears that, in SO emulsion sage polyphenols acted as

277 an emulsifier, by bridging between the hydrophobic oil phase and the hydrophilic caseinate-gum

278

14

arabic polymer phase entrapping oil molecules firmly inside the hydrophobic core. On the

279 otherhand, the slight phase separation observed in FO emulsion might be related to the random

280 protein–protein interaction induced by the shearing during homogenization (Koh, Chandrapala,

281 Zisu, Martin, Kentish, & Ashokkumar, 2014). In the present study, a single concentration of sage

282 extract was chosen for encapsulation studies, as 0.5% was found to be effective in protecting

283 emulsion from oxidation under accelerated storage studies (based on linoleic acid peroxidation

284 value: data not shown). However, considering the volatile nature of the extract, 1% level was

285 opted for encapsulation.

286 3.1.2. Emulsion microstructure 287 The emulsions prepared with and without sage extract were observed under an inverted

288 microscope and atomic force microscope. Both emulsions showed a homogeneous distribution of

289 oil droplets with good stability to aggregation or coalescence, when observed under an inverted

290 microscope (Figure 1A &B). It appears that there was an adequate number of wall polymer

291 (sodium caseinate and gum arabic) and oil molecules in the aqueous phase to form stabilized

292 emulsion droplets. Generally, formation of aggregates/flocculates of the wall polymers in

293 emulsions with high polymer content is expected. On the other hand, in cases where the wall

294 polymer is limiting, the excess oil comes out as coalescence (Dickinson, 2003). In the present

295 study, there was no evidence of these destabilizing phenomenons over a period of 1h when

296 observed under microscope. The SO emulsion showed more uniform sized particles with

297 predominance of smaller average droplet size (less than 2 µm) compared to a wide size range of

298 FO emulsion (3-10 ± 1.2 µm), which confers better interfacial stability to SO emulsion.

299 The Atomic Force Microscopic (AFM) image of emulsion droplets over as small

300 scanning area of 4 µm showed well-structured projections in SO emulsion, whereas FO emulsion

301

15

droplet showed more or less a flat image with uneven and less defined projections (Figure 1B &

302 D). Moreover, the mean diameter of the droplets in the scanned area was much less (0.5 nm) for

303 the SO emulsion compared to 13.44 nm for the FO emulsion. It is generally agreed that, small oil

304 droplets will be enclosed and embedded more efficiently within the wall matrix of the

305 microcapsules; hence, the resultant emulsion will be more stable during the spray drying process

306 which is one of the critical parameters to have the optimum efficiency (Sari et al., 2015). It

307 appears that presence of sage polyphenols created a compact configuration of oil droplets with

308 ordered network of wall polymers around the droplets, which could be densely packed at the

309 emulsion interface, as evidenced from microscopic images of fresh emulsion.

310 3.2. Characterisation of oil encapsulates 311 3.2.1. FT-IR spectra of encapsulates

312 In order to understand the nature of the interaction between wall polymers and polyphenols in

313 sage extract, FT-IR spectroscopic analysis of both the encapsulates were carried out (Figure 2).

314 Spectral behaviour of the samples was recorded in the region from 4000 - 400 cm–1, however, the

315 bands in the region 3600 – 1400 cm–1 were analyzed in detail, since they are characteristic of

316 bending and stretching vibrations of OH groups and NH groups that contribute significantly to

317 protein-protein/polyphenol-protein interaction through hydrogen bonding. Another region of

318 critical evaluation was 1800 - 1400 cm–1, characteristic of the bending vibrations of the same

319 groups. In the present study, the typical profile of casein was not observed as gum arabic was

320 also included as a co-polymer. The amide Ι (mainly C=O stretch) and II (C–N stretching coupled

321 with N–H bending modes) peaks for both FOE and SOE appeared at similar frequency of 1681- 322

1606 cm−1 and 1508 cm−1, respectively. However, amide-1 was slightly condensed in SOE. The

323

16

decrease in the intensity of the amide I band in the spectra suggests a major conformational

324 change introduced by the modification of terminal carboxyl groups of casein, in the presence of

325 polyphenols. Similar infrared spectral changes were observed for protein amide I band in casein- 326 tea polyphenol complexes where major protein conformational changes occurred (Hasni et al.,

327 2011). Coincidentally, a more pronounced ester group was detectable at 1744 cm−1 in SOE

328 compared to that in FOE, that might have resulted from the interaction of terminal carboxyl

329 group of casein/gum arabic with phenolic components. A major difference in the spectra

330 appeared near the NH stretching regions of amide-A and amide–B region, where only a single

331 distinct peak was evident in FOE at 3195 cm-1, which disappeared almost completely in SOE.

332 Apart from this, two minor peaks appeared at 2887 and 2969 cm-1 in FOE, were also present in

333 SOE with slight band shift towards lower wave numbers. A separate phenolic band could not be

334 detected in SOE, as it could be merged with that of phenolic amino acids in casein, however a

335 band shift from 1377 in FOE to 1396 cm-1 in SOE was observed, which might be attributed to

336 the O-H in plane deformation in polyphenol. Similarly, a minor band shift from 3585cm-1 in

337 FOE towards a higher wavenumber of 3604cm-1 was observed in SOE, suggesting a possible

338 modification of phenolic components. From the spectral changes observed in the present study,

339 the interaction between the wall polymers and sage polyphenols was evident in SOE sample. The

340 interactions between protein and polyphenols are mediated mainly through non-covalent

341 hydrogen and hydrophobic interactions, which alter the tertiary and secondary structure of

342 complex proteins as evidenced by the changes in characteristic absorption bands (Hasni et al.,

343 2011). In the present study, polymer cross linking through polyphenol complexing was expected

344 as these polyphenolic components contains multiple functional sites, which can introduce inter

345 and intrachain hydrogen bonds at many sites in polymer chains, in turn act as bridging molecules

346

17

for the protein/ carbohydrate polymers in the wall matrix. In addition to that, a covalent

347 interaction was postulated (Strauss, & Gibson, 2004), in which the diphenol moiety of a phenolic

348 acid or other polyphenols is readily oxidized to an orthoquinone in the presence of molecular

349 oxygen. The orthoquinone in turn forms a dimer in a side reaction, or reacts with amino or

350 sulfhydryl side chains of polypeptides to form covalent C–N or C–S bonds with the phenolic

351 ring, with regeneration of hydroquinone. The latter can be reoxidized and bind a second

352 polypeptide, resulting in a cross-link. Alternatively, two quinones, each carrying one chain, can

353 dimerize, also producing a cross-link. In SOE, the spectral change associated with amide-1,

354 appearance of a well-defined ester band and spectral shift in the phenolic band towards higher

355 wavenumber, all suggest wall polymer cross-linking mediated through polyphenol interactions.

356 3.2.2. Encapsulation efficiency (EE) and percentage loss during drying

357 The encapsulation efficiency reflects the degree of protection offered by the wall material

358 to oil droplets embedded within the wall material. As expected, SOE sample indicated higher EE

359 of 73.27% compared to 68.96% for FOE sample, which confirms the structural stabilization of

360 the wall matrix (network formed by wall material polymers) by polyphenols (Table 1). The

361 encapsulation efficiency of the process can be increased by applying higher inlet temperature

362 during drying, which leads to rapid crust formation around drying droplets and thereby giving

363 higher core retention. However, high temperature quite often results in collapse of encapsulates

364 leading to oil migration to the surface. This can be resolved by adding a suitable cross-linking

365 agent for the wall polymer, such as polyphenols for protein, which hastens the formation and

366 integrity of polymer crust. Several researchers (Liang, Shoemaker, Yang, Zhong, & Huang,

367 2013; Soottitantawat, Bigeard, Yoshii, Furuta, Ohkawara, & Linko, 2005) have observed an

368

18

inverse relationship between the emulsion droplet size and the retention of core material.

369 Accordingly, the higher encapsulation efficiency obtained for SOE could be related to the higher

370 emulsion stability, stronger crust formation and the smaller emulsion droplet size as compared to

371 that of FOE encapsulates.

372 The surface oil represents non-encapsulated oil and has been used as an important

373 parameter determining the quality of encapsulated products. In the present study, it was evident

374 from the FT-IR profile that even though the emulsions were kinetically stable at ambient

375 temperature, the elevated temperature and mechanical shearing during spray drying affected the

376 behaviour of wall polymers during atomisation. Accordingly, FOE showed significantly higher

377 surface oil content of 3.87 g/100 g of dry powder (31.01% of total oil content) as compared to

378 3.4 g/100 g of dry powder (26.79% of total oil content) for SOE (Table 1). Total oil is the total

379 amount of oil present in the encapsulate powder after spray drying. The TO registered a slightly

380 higher value of 12.72% of dry powder for SOE compared to 12.5% for FOE (Table 1), however

381 not statistically different indicating certain loss of oil during spray drying in both the emulsions

382 as compared to the total loaded quantity of oil in the emulsion (20% of total solid content). There

383 was only a negligible difference in the percentage loss of oil during spray drying between

384 encapsulates (Table 1), indicating the meagre loss of sage extract by volatilization during drying

385 phase. The slightly higher oil loss observed in FOE might be related to the higher content of free

386 oil, which is more susceptible to volatilisation during spray drying.

387 3.2.3. Morphology of microencapsulates 388 3.2.3.1. Scanning Electron Microscopy (SEM)

389

19

SEM images of encapsulates revealed distinct differences in size and surface regularity. A wide

390 range of particles having varying dimensions were observed for both the samples (Figure 3).

391 Among the two samples, the size variability was higher for FOE samples which suggests that the

392 atomized FO emulsion droplet was a mixture of intact polymer (which was not participated in oil

393 encapsulation), free oil droplets and oil encapsulates. On the otherhand, the microcapsules

394 incorporated with sage extract were more uniform in size and shape with good sphericity (Figure

395 3B), compared to FOE powder (Figure 3A). This indicates the stable structural interactions

396 between polyphenols in sage extract and the Na-caseinate-guar gum matrix polymers, and the

397 presence of higher proportion of oil encapsulates rather than intact polymer and free oil droplets.

398 Previously, fish oil co-encapsulated with phytosterols and limonene using whey protein isolate

399 and sodium caseinate as wall materials yielded good quality microcapsules, with higher retention

400 of EPA and DHA (Chen, Mcgillivrav, Wen, Zhong, & Quek, 2013). On the otherhand, in the

401 FOE sample, most of the capsules appeared to be collapsed with many large internal voids,

402 probably due to the mechanical stress induced by uneven drying at different parts of the droplets.

403 Wrinkles or dimples on the surface were observed in both the SOE and FOE encapsulates but

404 comparatively more in FOE encapsulates. This could possibly be due to the lower encapsulated

405 oil content of FOE allowing extensive shrinkage during the early stage of the drying process and

406 vacuole formation during later drying period. In SOE, the interaction between polyphenols in

407 sage extract and the polymer matrix resulted in fast crust formation, which was resistant to the

408 mechanical stress during spray drying. This inturn confirms the lower surface oil content

409 observed in SOE powder, as there was less opportunity for oil in the core to come out of the

410 capsules. Similarly, small agglomerates were visible in FOE, which could be due to the high

411 surface oil content that adhered the capsules together.

412

20

3.2.3.2. Atomic force microscopy (AFM) 413 The AFM images of SOE powder (Figure 3D) confirmed the higher encapsulation

414 efficiency and regular surface morphology of encapsulates compared to that of FOE (Figure 3C),

415 as represented by the evenly distributed projections/peaks in the SOE image. The spherical

416 encapsulates will be visible as peaks or elevations from the base, whereas the intact polymer and

417 the free oil will be visible as base aligned depressions. Conversely, the AFM image of FOE

418 indicated sparsely distributed uneven peaks on a continuous matrix/base, suggesting lesser

419 number of encapsulates in the composition. The size distribution obtained by AFM indicated the

420 formation of encapsulates near to nanoscale in both FOE and SOE samples. Even though, the

421 emulsion droplet size was considerably higher for FOE sample, the dried particles in the given

422 scanned area of 4µm were smaller in size (107 nm) than SOE (115 nm). This may be related to

423 the change in size composition of atomized droplets as well as the behaviour of wall polymers

424 during different phases of drying. The larger diameter of SOE particles confirms the formation of

425 proper orientation of wall polymers during spraying and formation of a thicker and denser crust

426 during drying with maximum retention of oil in the core, which increased the effective diameter

427 of the encapsulates. Accordingly in FOE, even though the droplet size was higher, the poor

428 stability of droplets during spray drying might have resulted in the shrinkage/collapse of the

429 capsule. Similar to the SEM image, a huge number of small aggregates were visible in the

430 topographical image of FOE samples, where as SOE powder remained as particles without

431 visible aggregates.

432 The height profile provides an estimate of the nature of the surface roughness. The

433 surface roughness of the encapsulates were evaluated and expressed in terms of their root-mean

434 square (RMS), Ra (average roughness) and Rsk (skewness) values extracted from height images

435

21

(Figure 3 C, D, inset). RMS indicates the deviation in the height of the evaluated object and can

436 be used to represent the roughness of a continuous surface (Yu & Ivanisevic, 2004). In the case

437 of encapsulated powder, the peaks or elevations from the base represent the presence of particles

438 or encapsulates in the scanned area. Hence, higher roughness values represent the presence of

439 more encapsulated particles in the given area. Both RMS and Ra indicated higher values for SOE

440 samples than FOE samples. Rsk values of both the samples yielded negative values, with higher

441 absolute value for FOE samples. In particular, a negative Rsk value of continuous surface means

442 that a larger number of valleys with respect to peaks are present on the surface profile, while a

443 positive Rsk value means that the presence of peaks is prevailing. The negative Rsk values

444 observed for samples may be due to the large discontinuity of the scanned area. Accordingly, the

445 lower EE and the formation of a lower number of regular capsules gives a lesser number of

446 elevations or peaks in the FOE samples, which results in the lower roughness values on

447 topographical scanning. The use of roughness values to characterize encapsulates is not

448 widespread, because of the large variability of roughness values of particulate surface calculated

449 from the height data. AFM generally gives accurate measurements for a material surface, rather

450 than for individual particles. The observations in the present study suggest AFM as a useful tool

451 for confirming the efficiency of encapsulation process along with other quantification

452 techniques.

453 3.2.4. Physical properties of encapsulates 454

3.2.4.1. Moisture content 455 Moisture content of fish oil encapsulates is an important parameter, as higher water

456 activity enhances lipid oxidation. Moreover, at higher moisture levels, the wall material changes

457

22

from the glassy state to amorphous rubbery state with a high molecular mobility, leading to the

458 release of encapsulated oil during storage (Velasco, Dobarganes, & Marquez-Ruiz, 2003). The

459 moisture content of FOE and SOE was found to be 5.91% and 5.01% respectively (Table 1). The

460 slightly lower moisture content observed in SOE encapsulates could be attributed to the higher

461 hydrophobicity imparted by sage extract to the encapsulate wall material. Furthermore, the

462 ordered network of wall material induced by the polyphenols in the extract facilitated the

463 distribution of water molecules in definite voids, facilitating easy moisture diffusion during the

464 drying process.

465 3.2.4.2. Bulk density 466 Bulk density is an important property of powdered products owing to functional and

467 economic reasons. High bulk density is desirable to reduce shipping and packaging costs while

468 very low bulk density influences other powder properties, such as flowability. The bulk density

469 of FOE and SOE encapsulates was 0.39 g/ml and 0.42 g/ml, respectively (Table 1), which is

470 higher than the values reported in literature for fish oil encapsulated with skimmed milk powder

471 (Aghbashlo, Mobli, Madadlou, & Rafiee, 2013). The difference in the bulk density value of

472 encapsulates can be related to difference in morphology of encapsulates, such as sphericity and

473 surface regularity of encapsulates. Spherical shaped particles with regular surface without any

474 dents or wrinkles can be more closely packed in a given volume, resulting in higher bulk density.

475 Accordingly, in the present study, the higher bulk density of SOE confirms the formation of

476 smooth and more regular encapsulates in SOE compared to that in FOE. Moreover, the higher

477 bulk density of SOE also suggests a better stability for SOE powder against oxidative

478 degradation compared to FOE powder. The higher the bulk density, the lesser the presence of

479

23

occluded air within the encapsulates and therefore, lesser the possibility of oxidative

480 deterioration of the core oil phase.

481 3.2.4.3. Hygroscopicity 482 Spray-dried particles can easily absorb water from the surrounding environment,

483 developing stickiness and caking during storage, unless necessary precautions are taken. Among

484 the two encapsulates, FOE showed a lower hygroscopicity value as compared to SOE (Table 1).

485 This might be due to the high surface oil content in the FOE as compared to the SOE. The

486 presence of non-encapsulated oil on the particle surface forms a hydrophobic layer thus reducing

487 the water absorption by encapsulates.

488 3.2.4.4. Colour 489 Accumulation of non-volatile decomposition products such as oxidized triacylglycerols

490 and free fatty acids during oxidation can lead to colour changes which indicate the extent of oil

491 deterioration in high fat containing foods. The colour of freshly encapsulated FOE was slightly

492 off-white in colour mainly imparted by gum arabic which is light brown in colour. Similarly,

493 freshly encapsulated SOE was slightly darker in colour due to the presence of sage extract which

494 is originally pale yellow-green in colour. There was distinct difference in the colour parameters

495 of FOE and SOE during different days of accelerated storage study (Table 1). Both the

496 encapsulated samples showed reduction in L* values during storage, however reduction was

497 minimum in SOE compared to FOE throughout the accelerated storage study at 60ºC.

498 The chroma parameters such as a* and b* values of all the samples showed marked

499 changes during storage. Both the freshly encapsulated powders showed positive a* values

500 indicating the nearness towards red chroma with significantly higher value for FOE sample. An

501

24

increase in redness of the fat containing formulation indicates the presence of fat oxidation

502 products. The b* values of all the samples showed positive values indicating the yellow chroma,

503 the intensity of which increased during storage. The higher yellowness values exhibited by FOE

504 during storage indicates the rapid oxidation of surface oil which yielded coloured secondary and

505 tertiary oxidation products.

506 3.2.5. In vitro release pattern of encapsulates in buffered saline

507 The in vitro release pattern of encapsulates in buffered saline containing alcohol

508 simulates the fate of encapsulates when incorporated in to a food system, especially when it

509 contains a nonpolar component like oil (emulsion) or protein precipitating agents like alcohol

510 (fermented products). The SOE showed a constant rate of oil release, which was less than 5% in

511 buffered saline for samples drawn at every I h interval, compared to 11-14% in FOE after first

512 hour of incubation (Figure 4), indicating the formation of wall matrices capable of conferring

513 better protection to SOE against surface disintegration and diffusion of oil into the food system.

514 The cumulative oil release over 4 h of incubation accounted 55.22% of total oil in FOE

515 compared to 19.74% in SOE. As there was a huge difference in the surface oil content of FOE

516 with the cumulative oil content in the buffered saline, the significantly higher rate of oil released

517 in FOE might be primarily related to the poor structural integrity of FOE encapsulates, resulting

518 in rapid diffusion of oil into the medium. Conversely in SOE, crosslinking reduced the mobility

519 of the polymer structure and enhanced its water resistance. Both the encapsulates showed

520 maximum rate of oil release during the initial 1 h followed by a linear pattern of release with

521 time. These results are consistent with the structural inferences derived from SEM and AFM

522 images.

523

25

3.2.6. In vitro gastro-intestinal digestion profile of microencapsulates

524 3.2.6.1. Effect of SGF and GIF on oil release 525

In order to assess the efficacy of microencapsulated fish oil for oral delivery or as a supplement

526 for targeted delivery of bioactives to specific parts of the gastro-intestinal tract (GIT), it is

527 imperative to test the stability and release behaviour of microencapsulates during GIT transit in

528 vitro before proceeding to in vivo trials (Kosaraju et al., 2006). Moreover, protein-polyphenol

529 interaction can also influence the digestion of proteins with the enzymes of the gastrointestinal

530 tract. The oil released after exposure to simulated gastric fluid was 71.71% and 64.26% of total

531 oil for FOE and SOE samples, respectively (Table 1). The release of oil from encapsulates

532 depends mainly on the extent of surface disintegration of wall matrix by acids and enzymes

533 present in the gastric fluids. The higher quantity of oil released from FOE might be attributed to

534 the presence of a comparatively higher number of broken encapsulates that allowed easy access

535 of enzymes and faster capsule degradation. For the same reason, the strong polymer matrix

536 formed in SOE encapsulates retarded the release of oil from microcapsules even in the gastric

537 fluid. On further exposure to simulated intestinal fluid, 15.41% of FOE and 14.98% of total oil of

538 SOE were released (Table 1). It is apparent that casein might have undergone structural

539 rearrangement under the low pH environment of gastric fluid containing the protease pepsin and

540 released most of the oil. However, the oil entrapped in the disintegrated/partially digested

541 polymer network is expected to release further at the intestine by the action of pancreatin, which

542 contains amylase to disintegrate gum arabic, and protease to hydrolyse casein. In-vivo human

543 clinical studies are required to understand the actual bioavailability of the oil from any designed

544 formulation. Also, release of oil to certain extent is expected to occur at colon by colonic fluid as

545 well as by the bacteria normally inhabiting the colon. In the present study, colonic release from

546

26

encapsulates has not been studied, as more than 80% of the oil loaded in encapsulates were

547 released in the GI tract itself. Moreover, the colon is one of the most difficult parts of the GI tract

548 to simulate in the laboratory as there exists a wide variation in the bacterial populations and it

549 requires cultivation of colonic bacteria under anaerobic conditions. Hence, many researchers

550 prefer to directly carry out tests on animal models (McClements, 2014).

551 3.2.6.2. Microscopic analysis of gastrointestinal digests

552 The encapsulates before and after digestion were observed using an inverted microscope

553 to confirm the inferences on the fate of the encapsulates in gastrointestinal tract. Both the

554 encapsulates showed aggregation and flocculate formation in the simulated fluids before

555 undergoing digestion (Figure 5 A&D). The structure of both encapsulates were destroyed

556 following in vitro digestion. After passing through the stomach phase, a reduction in droplet size

557 was observed due to hydrolysis of casinate-gum complex and weakening of electrostatic

558 repulsion (Figure 5 B&E). The digestion profiles revealed lower rate of aggregate formation in

559 gastric fluid for FOE (Figure 5 B) compared to SOE (Figure 5E), indicating the intense rupture

560 of capsules in FOE. However, as the digestion proceeded through the intestinal phase, both the

561 digest appeared more or less similar (Figure 5 C&F). The results suggest that fish oil

562 encapsulated within cross-linked microspheres would be digested more or less similar to those in

563 conventional fish oil encapsulates.

564 3.2.7. Measurement of lipid oxidation in microencapsulates

565 3.2.7.1. Measurement of PV 566 Inorder to ascertain the protective effect of sage extract against fat oxidation, the oxidative

567 pattern of encapsulates were compared against pure fish oil used for encapsulation (PFO) and

568

27

fish oil containing 1% sage extract (SFO). The protective effect of sage extract in standard

569 antioxidant in vitro assays was reported in our earlier report (Binsi et al., 2016). The PV of pure

570 fish oil was 4.56 meq of O2/kg oil, which increased considerably to 10.89 and 12.32 meq of

571 O2/kg oil in FOE and SOE, respectively (Figure 6A). This clearly shows that during spray

572 drying, oil particles underwent certain extent of oxidation before getting encapsulated, and

573 addition of antioxidant could not impart protection during this stage. However, the protective

574 effect of encapsulation was clearly visible during storage, as PFO showed more than ten-fold

575 increase in peroxide content after 24 h of storage. SFO also followed similar oxidative pattern of

576 PFO, however showed lower PV than PFO during storage. Both FOE and SOE samples showed

577 a progressive increase up to the 5thday with lower absolute values for SOE at any day of

578 sampling. Previously, sage extract at 0.02% was reported to be highly effective in protecting the

579 stability of rapeseed oil during accelerated oxidation storage conditions and was comparable

580 with that of butylated hydroxytoluene (BHT) at the same concentration (Bandoniene, Pukalskas,

581 Venskutonis, & Gruzdien., 2000). However, the results of the present study suggests a physical

582 mechanism of protection rather than the expected radical scavenging activities of polyphenols, as

583 the protection was more visible during storage rather than during spray drying. It is logical to

584 infer from the results of other parameters that the wall of SOE was more dense and protective

585 than that of FOE, which prevented further diffusion of bulk oil from the core to the surface apart

586 from offering barrier property against oxygen from surface to the core.

587 3.2.7.2. Measurement of Thiobarbituric acid reactive substances (TBARS)

588 The pure fish oil and encapsulated samples showed significant variation (p < 0.05) in TBARS

589 values under accelerated storage (Figure 6B). Both the encapsulates presented comparable initial

590

28

TBARS values of 1.03 and 0.92 for FOE and SOE respectively, whereas that of PFO and SFO

591 were significantly lower (p < 0.05). Homogenization of the emulsion involves intense

592 mechanical stress and turbulences, which on further exposure to high temperature during spray

593 drying leads to rapid oil oxidation. The TBARS value crossed the limit of 2 after 24 h of storage

594 in all the samples and showed almost similar values during the initial two days of storage. The

595 initial high values showed by all the samples may be related to the generation of secondary

596 oxidation products from the already existing peroxides in the samples. However, during further

597 storage the lowest rate of increase in TBARS value was observed in SOE sample, which was

598 even lower than SFO. Regarding the use of antioxidants in spray drying, Serfert, Drusch, &

599 Schwarz (2009) have inferred that antioxidants efficient in stabilizing liquid systems do not

600 necessarily increase the stability of oil encapsulated by spray-drying. However, the results of

601 present study shows that the protective effect can be fortified by incorporating antioxidants in the

602 oil, but the differences between oxidation rates might be related to the formation of an efficient

603 physical barrier at the interface. In other words, the enhancement of the stability is due to the

604 formation of a glassy state crust of sodium caseinate and gum arabic reducing the molecular

605 mobility of oxygen and thus slowing down the rate of lipid oxidation.

606 4. Conclusion 607 The purpose of the present study was to increase the structural and oxidative stability of spray

608 dried fish oil encapsulates by incorporating polyphenol rich sage extract as protein cross-linker

609 and as antioxidant to fish oil so as to minimize the effect of high temperature during spray

610 drying. FT-IR profile of the encapsulates confirmed the interaction of polyphenols with wall

611 polymers. Incorporation of sage extract improved the surface morphology and size uniformity of

612

29

encapsulates. Higher encapsulation efficiency and lower surface oil content in the encapsulated

613 products was achieved by incorporating sage extract at 1% level in the emulsion prior to spray

614 drying. The results of lipid oxidation parameters during accelerated storage study suggested a

615 physical mechanism of protection. Eventhough the total oil released was higher for FOE sample

616 during in vitro studies, the extent of protection offered by the sage extract against fat oxidation

617 and stability in normal food environment was significant. Hence, current findings shows that

618 incorporation of sage extract in fish oil before spray drying may be advocated. However, the

619 complete pattern of fish oil release in gastrointestinal tract could not be satisfactorily elucidated.

620 Further studies are required to enhance the release properties of encapsulates at targeted sites of

621 gastrointestinal tract.

622 Acknowledgment 623 This work was carried out under the research project funded by Science and Engineering

624 Research Board SERB (Department of Science and Technology, India – Ministry of Food

625 Processing Industries, India).

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715

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718 Yu, M., & Ivanisevic, A. (2004). Encapsulated cells: an atomic force microscopy

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723

724

725 726

35

LEGEND TO FIGURES 727

728

729

730 Figure 1.

A-B

Microscopic images of fish oil emulsions Inverted microscopic image: (A) FOE (B) SOE

Atomic force microscopic image: (C) FOE (D) SOE

Figure 2.

FT-IR profile of fish oil encapsulates

Figure 3.

A-D

SEM images of fish oil encapsulates (A) FOE and (B) SOE

AFM images of fish oil encapsulates (C) FOE and (D) SOE

Figure 4.

A-B

In vitro release profile of fish oil encapsulates

Figure 5 A-F

Optical microscopic images of gastro-intestinal digests of fish oil encapsulates (A) FOE before digestion (B) FOE after gastric digestion (C) FOE after gastric and intestinal digestion (D) SOE before digestion (E) SOE after gastric digestion (F) SOE after gastric and intestinal digestion

Figure 6 A-B Changes in PV and TBARS values of fish oil encapsulates and fish oil during accelerated storage study

FOE SOE

FOE SOE PFO SFO FOE SOE

Figure 1

A B C D

1509 3195 1744 2969 2966 1508 Figure 2 1745 Absorbance (%)

Wave number (cm-1) 3604 3585 1607 1606 FOE SOE

0 500 1000 1500 2000 2500 3000 3500 4000 3501

A B Figure 3 C RMS = 3.41; Ra= 2.87;Rsk =-0.84 D RMS = 5.15;Ra = 4.43; Rsk = -0.24

0 3 6 9 12 15 0 1 2 3 4 Cumulative release of fish oil (%)

Time (hr) FOE SOE Figure 4

C B A D E F Figure: 5

0 40 80 120 160 200 A 0 10 20 30 0 2 4 6 8 Storage period (Days)

PV (mEq O2/kg oil ) TBARS value (mg malonaldehyde/kg oil)

FOE SOE PFO SFO

Figure 6

42

881 Parameter FOE SOE Emulsion stability index (%)

96.66a* ±0.89 98.67 b±0.72 Microencapsulation efficiency (%)

68.99 a ±1.08 73.21 b ±1.10 Surface oil ( g/100 of dry powder )

3.87 a ±0.05 3.40 b ±0.06 Total oil (g/100 of dry powder)

12.50 a ±0.04 12.72 a ±0.03 Percentage loss during spray drying (as

% of loaded oil in emulsion) 33.57 a ±0.05 33.04 a ±0.09

Bulk density(g/ml) 0.39 a ±0.06 0.42 a ±0.11 Hygroscopicity (g/100g)

7.70 a ±0.15 8.39 b ±0.21 Moisture content (%) 5.91 a ±0.06

5.01 b ±0.04 Oil released by gastric fluid (% of total oil)

71.71 a ±0.88 64.26 b ±0.83 Oil released by intestinal fluid (% of total oil)

15.41 a ±0.21 14.98 b ±0.22 Total oil released (as % of total oil)

87.12 a ±0.93 79.24 b ±0.75 Unreleased oil (as % of total oil)

12.88 a ±0.16 20.76 b ±0.14 Storage Day Hunter-lab colour parameters of fish oil encapsulates during accelerated storage

FOE SOE 0 82.76±0.98 1.37±0.10 18.97±0.78 82.7±0.95

0.73±0.11 16.32±0.28 1 82.61±0.91 1.74±0.12 22.48±0.41

81.82±0.82 1.12±0.08 20.19±0.31 2 81.55±0.81 2.26±0.11

24.16±0.53 81.24±0.85 1.45±0.09 21.57±0.58 3 82.38±0.88 2.02±0.08

23.84±0.84 82.18±0.88 1.37±0.11 21.98±0.32 4 82.35±0.92 1.97±0.12

23.74±0.79 81.78±0.90 1.41±0.12 22.14±0.40 Table 1: Physicochemical and oil release properties of fish oil encapsulates

43

5 82.45±0.73 2.24±0.16 24.62±0.58 81.49±0.91 1.71±0.08

23.09±0.33 6 79.83±0.58 2.54±0.18 24.97±0.62 80.41±0.85

1.93±0.08 23.49±0.28 7 78.01±0.43 2.17±0.16 24.23±0.73

80.58±0.88 1.73±0.07 23.36±0.43

882

883

884 885 Values in parenthesis represents standard deviation for n=3;

*Treatment mean values with same letters are not significantly different from each other (p < 0.05).

44

Highlights 886 • Sage polyphenols along with gum arabic strengthened shell matrix

887 • Sage polyphenols improved encapsulation efficiency

888 • The stabilised structure reduced oil oxidation

889 • In vitro release kinetics confirmed controlled release of oil in modified encapsulates.

890

891

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# 已录用稿

## 阿拉伯胶与鼠尾草多酚对喷雾干燥鱼油微胶囊的结构与氧化稳定作用:表征与释放动力学

P.K. Binsi, Natasha Nayak, P.C. Sarkar, A. Jeyakumari, P. Muhamed Ashraf, George Ninan, C.N. Ravishankar

**PII:** S0308-8146(16)31521-7 **DOI:** http://dx.doi.org/10.1016/j.foodchem.2016.09.126 **文献编号:** FOCH 19906 **待发表于:** Food Chemistry **收稿日期:** 2016年4月18日 **修回日期:** 2016年8月13日 **录用日期:** 2016年9月19日

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## 阿拉伯胶与鼠尾草多酚对喷雾干燥鱼油微胶囊的结构与氧化稳定作用:表征与释放动力学

Binsi PK¹*, Natasha Nayak¹, Sarkar PC², Jeyakumari A³, Muhamed Ashraf P¹, George Ninan¹, Ravishankar CN¹

¹ 印度农业研究理事会-中央渔业技术研究所(CIFT),Matsyapuri, Willington Island, Cochin, India – 682 029 ² 印度农业研究理事会-天然树脂与树胶研究所,Namkum, Ranchi-834 010 ³ 印度农业研究理事会-CIFT孟买研究中心,Sector-1, Vashi, Navi Mumbai, Maharashtra 400 703

*通讯作者 电话: ++ 91-484 - 2412300 传真: ++ 91 - 484 – 2668212 电子邮箱: binsipk@yahoo.com

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## 摘要

本研究评估了阿拉伯胶与鼠尾草多酚在喷雾干燥过程中协同稳定胶囊壁、保护鱼油微胶囊免受热致破坏和氧化劣变的功效。以酪蛋白酸钠为壁材聚合物、阿拉伯胶为壁材共聚物、鼠尾草提取物为壁材稳定剂制备乳液,采用单流体喷嘴进行喷雾干燥。与仅含阿拉伯胶的微胶囊(FOE)相比,以阿拉伯胶和鼠尾草提取物稳定的鱼油微胶囊(SOE)表现出显著更高的包埋效率。扫描电子显微镜和原子力显微镜图像显示,与FOE粉末相比,SOE微胶囊粒径均匀、球形度良好且表面光滑。微胶囊的体外油释放实验表明,在缓冲盐溶液中油释放量可忽略不计,而在模拟胃肠道液中,微胶囊中负载的80%以上油脂被释放。含鼠尾草提取物的微胶囊在贮藏期间表现出较低的脂质氧化速率。

**关键词:** 鱼油微胶囊;氧化;鼠尾草提取物;多酚

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## 1. 引言

Omega-3脂肪酸(如二十碳五烯酸EPA和二十二碳六烯酸DHA)的健康益处主要源于其抗炎和抗心律失常特性,对心脏功能具有保护作用(Endo, & Arita, 2016)。流行病学研究表明,高鱼类摄入量与认知障碍、抑郁以及痴呆或阿尔茨海默病的发生呈负相关(Freund-Levi et al., 2014)。尽管具有这些健康益处,膳食摄入富含Omega-3的鱼油仍存在一定的食品安全隐患。Omega-3脂肪酸极易发生氧化变化,产生有毒的次级和三级氧化产物,这限制了鱼油在食品(尤其是婴幼儿配方食品)中的直接消费量或添加量。

将鱼油包埋在稳定的壁材基质中进行微胶囊化已被认为是递送鱼油补充剂的有效技术,因为该方法可减少氧化劣变并提高生物利用度。在鱼油微胶囊化的各种技术中,喷雾干燥是最经济的方法,其成本比冷冻干燥低30-50倍(Gharsallaoui, Roudaut, Chambin, Voilley, & Saurel, 2007)。然而,操作温度较高以及雾化过程中的机械剪切力是微胶囊化过程中的主要挑战,因为这些作用力可能破坏乳液稳定性,并在干燥过程中促进胶囊塌陷以及鱼油氧化。因此,由于壁材形成材料之间的离子相互作用本身不能保证所得微胶囊的结构完整性,交联剂的使用往往成为必要手段(Koupantsis, Pavlidou, & Paraskevopoulou, 2016)。目前,甲醛、戊二醛以及酶转谷氨酰胺酶已被用作蛋白质交联剂。然而,由于醛类物质对健康和环境的不利影响,以及酶介导工艺的经济可行性较低,对天然且经济可持续的替代方案的需求很高。因此,在乳液中添加天然交联剂和抗氧化剂是非常可取的,尤其是在涉及喷雾干燥时。

在正确的时间和地点控制释放食品成分是微胶囊化可提供的另一项关键功能。通常,基于碳水化合物和蛋白质的微胶囊是水溶性的,因此不适合控释应用(Cho, Shim, & Park, 2003)。然而,如果蛋白质被交联成稳定形式,蛋白质作为壁材的应用将大大增加,可用于敏感补充剂的靶向和控释递送。交联改变了蛋白质分子的净电荷,因此可用于改变蛋白质在特定介质中的溶解模式。这具有额外的技术优势,即微胶囊可同时作为Omega-3鱼油和蛋白质的补充剂。

富含多酚的植物精油具有多种功能,是包埋鱼油壁材的理想选择,因为它们既是有效的蛋白质交联剂,又可作为鱼油的强效抗氧化剂,发挥还原剂或单线态氧清除剂的作用。已知多酚在氧化条件下与肽的侧链氨基反应,导致蛋白质交联的形成,如明胶-果胶微粒在与咖啡和葡萄汁中的多酚交联后,表现出增强的亲脂性和抗热降解能力(Strauss, & Gibson, 2004)。同样,据报道单宁酸对肌原纤维蛋白具有显著的交联能力(Prodpran, Benjakul, & Phatcharat, 2012)。植物多酚化合物也与乳蛋白(如酪蛋白)表现出强相互作用。此前已有报道,通过使用甘油和单宁酸对酪蛋白酸钠或乳清蛋白分离物-羧甲基纤维素微胶囊进行交联强化胶囊壁(Koupantsis et al., 2016)。蛋白质与植物酚类之间的相互作用主要通过大量氢键桥联的非共价相互作用进行聚合(Frazier et al., 2010),以及通过共价C-N或C-S键形成(Strauss, & Gibson, 2004)。鼠尾草(Salvia sp.)等草药被美国食品药品监督管理局(USFDA)列入"香料及其他天然调味料和调味剂"类别,属于公认安全物质。鼠尾草的抗氧化活性主要与两种酚类二萜——鼠尾草酸和鼠尾草酚有关,它们是有效的自由基清除剂(Dorman, Peltoketo, Hiltunen, & Tikkanen, 2003)。阿拉伯胶因其胶体功能以及与大多数常用作壁材聚合物的碳水化合物和蛋白质的相容性,是包埋鱼油和其他植物油的常用试剂。然而,迄今为止尚未评估草药提取物对鱼油微胶囊结构稳定性的功效。因此,本研究的目的是评估鼠尾草提取物和阿拉伯胶对鱼油微胶囊结构和氧化稳定性的功效,重点在于最大限度地减少喷雾干燥过程中高温和机械剪切力的不利影响。此外,还评估了微胶囊在加速氧化气氛下的氧化稳定性以及在缓冲盐溶液和胃肠道环境中的油脂释放模式。

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## 2. 材料与方法

### 2.1. 原材料

阿拉伯胶(来源于Acacia Senegal,平均分子量285 kDa,含蛋白质<1%、不溶物<1%)、胃蛋白酶(活性800-2500 ml单位/mg蛋白质)和胰酶4NF(均为猪源)购自Hi-Media Pvt Ltd.(印度孟买)。特级酪蛋白酸钠购自Sisko Research Laboratories Pvt. Ltd.(印度孟买)。用于微胶囊制备的鱼油提取自印度沙丁鱼(Sardinella longiceps),其脂肪酸组成已知(肉豆蔻酸:11.98%,硬脂酸:4.88%,棕榈酸:23.66%,棕榈油酸:13.22%,油酸:8.55%,EPA:13.55%,DHA:10.42%)。含45%(w/w)精油的鼠尾草(Salvia officinalis)提取物购自Synthite Industries Ltd.(印度科钦)。通过气相色谱-质谱联用(GC-MS-MS)分析确定的鼠尾草提取物组成如下:1,8-桉叶素(12.8%)、α-葎草烯(11.8%)、绿花白千层醇(11.1%)、β-石竹烯(5.8%)、α-侧柏酮(4.2%)、β-侧柏酮(4.1%)、香芹酚(3.6%)、百里酚(3.4%)、β-蒎烯(3.3%)、α-蒎烯(3.1%)、樟脑(3.1%)、柠檬烯(2.8%)、冰片(2.5%)、芳樟醇(2.1%)、绿花白千层烯(2.1%)、月桂烯(1.9%)、对伞花烃(1.2%)、乙酸芳樟酯(1.1%)、莰烯(0.9%)、14-羟基-9-表-(E)-石竹烯(0.8%)、石竹烯氧化物(0.7%)、γ-杜松烯(0.7%)、δ-杜松烯(0.6%)、香橙烯(0.4%)。

### 2.2. 乳液的制备

喷雾干燥乳液的组成基于我们先前报道的结果确定(Jeyakumari, Janarthanan, Chouksey, & Venkateshwarlu, 2014)。通过24小时内定量相分离和乳液液滴的显微观察确认乳液的稳定性。相应地,制备总固形物含量为7.5%的乳液,其中酪蛋白酸钠、阿拉伯胶和鱼油的比例为2:2:1(即100 ml乳液中含3 g酪蛋白酸钠、3 g阿拉伯胶和1.5 g鱼油)。制备两种不同的乳液配方用于包埋,即鱼油乳液(FO乳液)和含1%鼠尾草提取物(以鱼油重量计)的鱼油乳液(SO乳液),保持总固形物含量恒定为7.5%。乳液的制备方法为:将酪蛋白酸钠溶于40°C水浴中并间歇搅拌,待充分溶解后冷却,在不断搅拌下加入阿拉伯胶以避免结块。壁材溶解后,将预先与1%鼠尾草提取物混合的鱼油加入溶液中。混合物采用高速均质机(Poly system PT 2100, Kinematica, AG)在25000 rpm下均质5 min。喷雾干燥前,乳液在4°C下稳定1 h。

### 2.3. 乳液的喷雾干燥

喷雾干燥采用中试规模喷雾干燥机(Hemraj Pvt Ltd, 印度孟买),雾化喷嘴直径0.5 mm,压力450 kPa。进风和出风温度分别保持在160°C和80°C,进料速率调节为15-22 g/min。由FO乳液和SO乳液制备的微胶囊粉末分别命名为FOE和SOE。对两种乳液各进行了三次独立的包埋试验。

### 2.4. 乳液的表征

#### 2.4.1. 乳液稳定性指数(ESI)

将约150 ml各样品转移至250 ml量筒中,在4°C下静置24 h。24 h后测量未分离相的体积,以稳定性指数表示乳液稳定性:

ESI (%) = (H₁ / H₀) × 100

其中:H₀代表乳液初始体积,H₁为未分离相体积。

#### 2.4.2. 乳液微观结构

通过将乳液样品涂抹在载玻片上进行显微镜观察,使用倒置显微镜(Leica Microsystems, 德国Wetzlar)和非接触模式原子力显微镜(XE-100, Park Systems, 韩国)分析乳液微观结构,采用硅探针。乳液新鲜制备后在室温(25°C)下进行分析。倒置显微镜观察在200倍放大下获取图像,使用图像处理软件(Leica Microsystems Imaging Solutions, 英国Cambridge)配合CCD相机测定5个主要尺寸液滴的平均粒径。AFM分析时,将10 µl乳液样品直接滴加在硅片上,风干后在4 µm扫描面积内进行分析。

### 2.5. 微胶囊的分析

#### 2.5.1. 傅里叶变换红外光谱分析(FTIR)

喷雾干燥后立即使用Thermo Fisher Scientific FT-IR光谱仪(型号Nicolet™ iS™ 10, Thermo Fisher Scientific, 美国Waltham, MA)对两种微胶囊进行FTIR分析,采用KBr压片法,波长范围为4000-400 cm⁻¹。使用OMNIC软件(Thermo Fisher Scientific)分析光谱。

#### 2.5.2. 包埋效率(EE)和油脂损失百分率的测定

喷雾干燥粉末的表面油采用正己烷提取,参照已有方法(Dieffenbacher & Lüthi, 1986)稍作修改。将1 g粉末与10 ml正己烷在带塞的100 ml锥形瓶中混合,在25°C下振荡2.5 h,然后通过Whatman 4号滤纸过滤。收集的溶剂蒸发后,通过重量法测定表面油含量。总油从原始粉末中提取,而包埋油则在提取游离油后从残余干燥粉末中提取。分别取约0.5 g原始粉末和残余干燥粉末,与4 ml 2 M盐酸水溶液混合,在95°C下煮沸30 min。冷却后,加入2 ml乙醇并剧烈振荡。然后加入10 ml石油醚,混合物在25°C下以9000 rpm离心5 min。将上层转移并在105°C烘箱中干燥,通过重量法测定样品中的油脂含量。

包埋效率(EE%)按Wang, Liu, Chen, & Selomulya(2016)所述公式计算:

EE (%) = [(TO - SO) / TO] × 100

其中,TO为每克微胶囊粉末中的总油含量(以干重计),SO为每克微胶囊粉末中的表面油含量(以干重计)。

喷雾干燥过程中的损失百分率基于微胶囊中的总油含量和乳液中每克壁材聚合物所负载的油量(以干重计)计算:

损失 (%) = [(LO - TO) / LO] × 100

其中,LO为乳液中每克总固形物所负载的总油量(酪蛋白酸钠、阿拉伯胶和油的总重量),此处LO = 0.20 g油/g固形物重量。

#### 2.5.3. 微胶囊的形貌

##### 2.5.3.1 扫描电子显微镜(SEM)

通过SEM(XL 30 Philips, 荷兰)观察FOE和SOE微胶囊的表面外观和形貌。样品固定在安装在SEM样品台的双面导电碳胶上,在溅射镀膜仪中镀金后进行SEM观察。

##### 2.5.3.2 原子力显微镜(AFM)

采用非接触模式原子力显微镜(使用硅探针)研究FOE和SOE微胶囊的形貌,分析方法与乳液液滴分析类似。将样品(100 mg)分散在蒸馏水(10 ml)中,使用探头超声仪超声分散。将10 µl分散样品滴加在硅片上,风干后分析其表面特征。

#### 2.5.4. 微胶囊的物理性质

##### 2.5.4.1 水分含量的测定

微胶囊水分含量按AOAC方法测定(AOAC, 2000)。

##### 2.5.4.2 堆积密度的测定

简言之,将2 g粉末松散装入10 ml量筒中,记录体积。粉末的堆积密度通过样品重量除以其体积计算。

##### 2.5.4.3 吸湿性

将1 g样品置于含NaCl饱和溶液(相对湿度75.3%)的干燥器中。一周后称量样品,吸湿性以每100 g样品吸收的水分量表示(g/100 g)。

#### 2.5.5. 微胶囊的油脂释放特性

##### 2.5.5.1 微胶囊在缓冲盐溶液中的释放特性

参照Hosseini, Zandi, Rezaei, & Farahmandghavi(2013)的方法分析微胶囊在缓冲盐溶液中的释放动力学。将微胶囊(20 mg)置于含5 ml 60%磷酸盐缓冲液(pH 7.4)和40%乙醇的离心管中。混合物在室温(27±2°C)下温和振荡孵育。每隔1 h,样品在25°C下以9000 rpm离心5 min。吸取一定体积的上清液进行分析,并替换等体积的新鲜培养基。根据分别针对鱼油在215 nm处和含1%鼠尾草提取物的鱼油在275 nm处获得的标准曲线(由各自吸收光谱获得),使用紫外-可见分光光度计测定各取样时间点介质中累积释放的油脂量。鱼油累积释放百分率通过各取样时间点累积释放的油脂量(Mt)除以微胶囊中油脂总重量(Mo)获得:

累积释放 (%) = (Mt / Mo) × 100

##### 2.5.5.2 模拟胃肠道液中油脂释放的体外消化动力学

模拟胃液(SGF,含胃蛋白酶)和模拟肠液(SIF,含胰酶)按美国药典(2000)方法制备。对于SIF,如Kosaraju, D'Ath, & Lawrence(2006)针对包埋鱼油所建议的,由于所用样品为干粉,胰酶浓度提高了10倍。将微胶囊(5.0 g)先在37°C、100 rpm条件下进行胃消化2 h。随后加入SIF,在相同条件下继续肠消化3 h。微胶囊暴露于SGF和SIF后释放的油脂量分别按Patten, Augustin, Sanguansri, Head, & Abeywardena(2009)的方法测定。消化前后微胶囊的微观结构分别使用倒置显微镜(Leica Microsystems, 德国Wetzlar)在室温(25°C)下200倍放大直接观察乳液样品进行监测。

#### 2.5.6. 加速贮藏研究测定微胶囊中的脂质氧化

##### 2.5.6.1 脂质氧化产物的测定

通过60°C加速贮藏7天(使用热风烘箱)评估微胶囊的氧化稳定性。将微胶囊(约30 g)置于密封玻璃瓶中,用铝箔覆盖以避免光照。同时分析用于包埋的纯鱼油(PFO,30 g)以进行比较。微胶囊的过氧化值(PV)按Shantha和Decker(1994)所述方法在特定时间间隔测定。样品中氢过氧化物浓度使用异丙苯氢过氧化物标准曲线测定,以每千克负载油脂的mEq O₂表示。乳液次级氧化产物的变化通过测定硫代巴比妥酸反应物(TBARS)确定,按McDonald和Hultin(1987)所述方法进行,以每千克粉末的丙二醛毫克数表示。

##### 2.5.6.2 色泽

微胶囊的色泽使用Hunter Lab色差计(Color Flex, Hunter Lab Inc., 美国Reston, VA)测定。将样品装入64 mm玻璃样品杯中至预定水平,测定L*、a*和b*参数。

#### 2.5.7. 统计分析

所得数据采用SPSS软件16.0版(SPSS Inc, 美国芝加哥)进行单因素方差分析(ANOVA)。所有均值分离在95%显著性水平(p<0.05)下进行。

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## 3. 结果与讨论

### 3.1. 乳液的表征

#### 3.1.1. 乳液稳定性指数

获得稳定的液体乳液是喷雾干燥粉末中实现适当包埋的前提条件。我们先前的研究表明,酪蛋白酸钠与具有表面活性的阿拉伯胶可形成稳定的鱼油乳液,无可见相分离(Jeyakumari et al., 2014)。在本研究中,喷雾干燥前确认了含与不含鼠尾草提取物乳液在24小时内的稳定性。结果表明,两种乳液均具有动力学稳定性,FO乳液和SO乳液的未分离相分数分别为96.66%和98.67%(表1)。多项研究推断,鱼油乳液的性质和稳定性在很大程度上受微量成分(尤其是乳化剂)含量的影响(Jiménez-Martín, Gharsallaoui, Pérez-Palacios, Carrascal, & Rojas, 2015; Komaiko, Sastrosubroto, & McClements, 2016)。在SO乳液中,鼠尾草多酚似乎起到了乳化剂的作用,通过桥接疏水性油相和亲水性酪蛋白酸钠-阿拉伯胶聚合物相,将油分子牢固地包裹在疏水核心内。另一方面,FO乳液中观察到的轻微相分离可能与均质过程中剪切力诱导的随机蛋白质-蛋白质相互作用有关(Koh, Chandrapala, Zisu, Martin, Kentish, & Ashokkumar, 2014)。在本研究中,选择单一浓度的鼠尾草提取物用于包埋研究,因为0.5%的浓度在加速贮藏研究中已被证明能有效保护乳液免受氧化(基于亚油酸过氧化值:数据未显示)。然而,考虑到提取物的挥发性,选择1%的水平用于包埋。

#### 3.1.2. 乳液微观结构

在倒置显微镜和原子力显微镜下观察含与不含鼠尾草提取物的乳液。在倒置显微镜下观察时,两种乳液均显示出油滴的均匀分布,具有良好的抗聚集或聚结稳定性(图1A和B)。这表明水相中有足够数量的壁材聚合物(酪蛋白酸钠和阿拉伯胶)和油分子形成稳定的乳液液滴。通常,在聚合物含量高的乳液中,预期会形成壁材聚合物的聚集体/絮凝物。另一方面,在壁材聚合物不足的情况下,多余的油会以聚结形式析出(Dickinson, 2003)。在本研究中,在显微镜下观察1小时内未发现这些不稳定现象的证据。与粒径分布范围较宽的FO乳液(3-10 ± 1.2 µm)相比,SO乳液显示出更均匀的粒径,且较小平均粒径(小于2 µm)占主导地位,这赋予SO乳液更好的界面稳定性。

原子力显微镜(AFM)在4 µm小扫描面积下对乳液液滴的成像显示,SO乳液呈现结构良好的突起,而FO乳液液滴图像相对平坦,突起不均匀且轮廓不清晰(图1B和D)。此外,扫描区域内SO乳液液滴的平均直径(0.5 nm)远小于FO乳液(13.44 nm)。通常认为,小油滴将被更有效地包裹和嵌入微胶囊的壁材基质中;因此,所得乳液在喷雾干燥过程中将更加稳定,这是获得最佳效率的关键参数之一(Sari et al., 2015)。鼠尾草多酚的存在似乎使油滴形成了致密的结构,壁材聚合物在液滴周围形成有序的网络,如新鲜乳液的显微图像所证实的,这些聚合物可在乳液界面处密集堆积。

### 3.2. 油脂微胶囊的表征

#### 3.2.1. 微胶囊的FT-IR光谱

为了了解壁材聚合物与鼠尾草提取物中多酚之间相互作用的性质,对两种微胶囊进行了FT-IR光谱分析(图2)。样品的光谱行为记录在4000-400 cm⁻¹区域,但详细分析了3600-1400 cm⁻¹区域的谱带,因为这些区域是OH和NH基团弯曲和伸缩振动的特征区域,通过氢键对蛋白质-蛋白质/多酚-蛋白质相互作用有显著贡献。另一个关键评估区域是1800-1400 cm⁻¹,同样是这些基团弯曲振动的特征区域。在本研究中,由于阿拉伯胶也作为共聚物加入,未观察到典型的酪蛋白光谱特征。FOE和SOE的酰胺I(主要为C=O伸缩振动)和酰胺II(C-N伸缩耦合N-H弯曲振动)峰分别出现在相似的频率1681-1606 cm⁻¹和1508 cm⁻¹处。然而,SOE中的酰胺I略有凝聚。光谱中酰胺I带强度的降低表明,在多酚存在下,酪蛋白末端羧基的修饰引入了主要的构象变化。在酪蛋白-茶多酚复合物中观察到类似的蛋白质酰胺I带红外光谱变化,其中发生了主要的蛋白质构象变化(Hasni et al., 2011)。巧合的是,与FOE相比,SOE在1744 cm⁻¹处检测到更明显的酯基,这可能是由酪蛋白/阿拉伯胶的末端羧基与酚类组分相互作用产生的。光谱中的一个主要差异出现在酰胺A和酰胺B区域的NH伸缩振动附近,FOE中仅在3195 cm⁻¹处出现一个明显的单峰,而在SOE中几乎完全消失。此外,FOE中在2887和2969 cm⁻¹处的两个次要峰在SOE中也存在,仅向低波数方向略有偏移。由于SOE中的酚类谱带可能与酪蛋白中的酚类氨基酸谱带重叠而无法单独检测到,但观察到从FOE的1377 cm⁻¹到SOE的1396 cm⁻¹的谱带偏移,这可能归因于多酚中O-H的面内变形。同样,观察到FOE中3585 cm⁻¹处的次要谱带在SOE中向高波数方向偏移至3604 cm⁻¹,表明酚类组分可能发生了修饰。从本研究观察到的光谱变化来看,SOE样品中壁材聚合物与鼠尾草多酚之间的相互作用是显而易见的。蛋白质与多酚之间的相互作用主要通过非共价的氢键和疏水相互作用介导,这改变了复合蛋白质的三级和二级结构,特征吸收带的变化即为证据(Hasni et al., 2011)。在本研究中,预期会发生通过多酚络合的聚合物交联,因为这些多酚组分含有多个功能位点,可在聚合物链的许多位点引入链间和链内氢键,从而充当壁材基质中蛋白质/碳水化合物聚合物的桥联分子。此外,还推测存在共价相互作用(Strauss, & Gibson, 2004),其中酚酸或其他多酚的二酚基团在分子氧存在下容易被氧化为邻醌。邻醌在副反应中形成二聚体,或与多肽的氨基或巯基侧链反应,与酚环形成共价C-N或C-S键,同时再生氢醌。后者可被重新氧化并结合第二条多肽链,形成交联。或者,各携带一条链的两个醌可二聚化,同样产生交联。在SOE中,与酰胺I相关的光谱变化、明确定义的酯带的出现以及酚类谱带向高波数的偏移,均表明通过多酚相互作用介导的壁材聚合物交联。

#### 3.2.2. 包埋效率(EE)和干燥过程中的损失百分率

包埋效率反映了壁材材料对嵌入其中的油滴的保护程度。正如预期,SOE样品的EE为73.27%,高于FOE样品的68.96%,这证实了多酚对壁材基质(壁材聚合物形成的网络)的结构稳定作用(表1)。该工艺的包埋效率可通过在干燥过程中施加更高的进风温度来提高,这导致干燥液滴周围快速形成外壳,从而提高芯材保留率。然而,高温往往导致微胶囊塌陷,使油脂迁移至表面。这可以通过为壁材聚合物添加合适的交联剂(如蛋白质的多酚)来解决,这加速了聚合物外壳的形成和完整性。多位研究者(Liang, Shoemaker, Yang, Zhong, & Huang, 2013; Soottitantawat, Bigeard, Yoshii, Furuta, Ohkawara, & Linko, 2005)观察到乳液液滴尺寸与芯材保留率之间存在反比关系。因此,SOE获得的较高包埋效率可能与更高的乳液稳定性、更强的外壳形成以及更小的乳液液滴尺寸有关,与FOE微胶囊相比具有优势。

表面油代表未包埋的油脂,已被用作确定包埋产品质量的重要参数。在本研究中,从FT-IR光谱可以明显看出,尽管乳液在室温下具有动力学稳定性,但喷雾干燥过程中的高温和机械剪切力影响了壁材聚合物在雾化过程中的行为。因此,FOE的表面油含量显著较高,为3.87 g/100 g干粉末(占总油含量的31.01%),而SOE为3.4 g/100 g干粉末(占总油含量的26.79%)(表1)。总油是喷雾干燥后微胶囊粉末中存在的油脂总量。SOE的总油含量略高,为干粉末的12.72%,而FOE为12.5%(表1),但无统计学差异,表明两种乳液在喷雾干燥过程中均有一定量的油脂损失,与乳液中负载的总油量(总固形物含量的20%)相比有所减少。微胶囊之间喷雾干燥过程中的油脂损失百分率差异极小(表1),表明干燥阶段鼠尾草提取物因挥发造成的损失微乎其微。FOE中观察到的略高油脂损失可能与较高的游离油含量有关,游离油在喷雾干燥过程中更易挥发。

#### 3.2.3. 微胶囊的形貌

##### 3.2.3.1 扫描电子显微镜(SEM)

微胶囊的SEM图像显示出尺寸和表面规则性的明显差异。两种样品均观察到具有不同粒径的宽范围颗粒(图3)。在两个样品中,FOE样品的尺寸变异性更高,这表明雾化的FO乳液液滴是未参与油包埋的完整聚合物、游离油滴和油微胶囊的混合物。另一方面,添加鼠尾草提取物的微胶囊尺寸和形状更均匀,球形度良好(图3B),与FOE粉末(图3A)相比具有优势。这表明鼠尾草提取物中的多酚与酪蛋白酸钠-阿拉伯胶基质聚合物之间存在稳定的结构相互作用,且油微胶囊的比例较高,而非完整聚合物和游离油滴。此前,使用乳清蛋白分离物和酪蛋白酸钠作为壁材,将鱼油与植物甾醇和柠檬烯共包埋,获得了高质量的微胶囊,EPA和DHA的保留率较高(Chen, Mcgillivrav, Wen, Zhong, & Quek, 2013)。另一方面,在FOE样品中,大多数胶囊似乎已塌陷,内部存在许多大空隙,可能是由于液滴不同部位干燥不均匀引起的机械应力所致。SOE和FOE微胶囊表面均观察到皱纹或凹陷,但FOE微胶囊中相对更多。这可能是由于FOE的包埋油含量较低,允许在干燥过程早期发生广泛收缩,以及在干燥后期形成空泡。在SOE中,鼠尾草提取物中的多酚与聚合物基质之间的相互作用导致快速形成外壳,该外壳在喷雾干燥过程中具有抗机械应力的能力。这反过来证实了SOE粉末中观察到的较低表面油含量,因为核心油脂从胶囊中渗出的机会较少。同样,在FOE中可见小的团聚体,这可能是由于较高的表面油含量使胶囊粘附在一起所致。

##### 3.2.3.2 原子力显微镜(AFM)

SOE粉末的AFM图像(图3D)证实了与FOE(图3C)相比,微胶囊具有更高的包埋效率和规则的形貌,SOE图像中均匀分布的突起/峰值即表明了这一点。球形微胶囊在基底上方显示为峰值或突起,而完整聚合物和游离油则显示为与基底对齐的凹陷。相反,FOE的AFM图像显示在连续基质/基底上稀疏分布着不均匀的峰值,表明组成中微胶囊数量较少。AFM获得的尺寸分布表明,FOE和SOE样品中形成的微胶囊接近纳米级。尽管FOE样品的乳液液滴尺寸相当大,但在给定的4 µm扫描面积内,FOE的干燥颗粒尺寸(107 nm)小于SOE(115 nm)。这可能与雾化液滴尺寸组成的变化以及壁材聚合物在不同干燥阶段的行为有关。SOE颗粒的较大直径证实了喷雾过程中壁材聚合物形成了适当的取向,并在干燥过程中形成了更厚、更致密的外壳,使核心油脂的保留率最大化,从而增加了微胶囊的有效直径。相应地,在FOE中,尽管液滴尺寸较大,但喷雾干燥过程中液滴的稳定性较差可能导致胶囊收缩/塌陷。与SEM图像类似,FOE样品的地形图像中可见大量小团聚体,而SOE粉末保持为颗粒状态,无明显团聚体。

高度轮廓提供了表面粗糙度性质的估计。对微胶囊的表面粗糙度进行了评估,并从高度图像中提取了均方根(RMS)、Ra(平均粗糙度)和Rsk(偏度)值来表示(图3 C、D,插图)。RMS表示评估对象高度的偏差,可用于表示连续表面的粗糙度(Yu & Ivanisevic, 2004)。对于包埋粉末,基底上方的峰值或突起表示扫描区域内颗粒或微胶囊的存在。因此,较高的粗糙度值表示给定区域内存在更多的包埋颗粒。RMS和Ra均显示SOE样品的值高于FOE样品。两个样品的Rsk值均为负值,FOE样品的绝对值较高。特别是,连续表面的负Rsk值表示表面轮廓上相对于峰值存在更多的谷值,而正Rsk值表示峰值占主导地位。样品观察到的负Rsk值可能是由于扫描区域的大面积不连续性所致。因此,FOE样品中较低的EE和较少规则胶囊的形成导致地形扫描中较少的突起或峰值,从而产生较低的粗糙度值。由于从高度数据计算出的颗粒表面粗糙度值变异性较大,使用粗糙度值表征微胶囊并不普遍。AFM通常对材料表面而非单个颗粒给出准确测量。本研究的观察表明,AFM作为一种有用工具,可与其他定量技术结合使用,用于确认包埋工艺的效率。

#### 3.2.4. 微胶囊的物理性质

##### 3.2.4.1 水分含量

鱼油微胶囊的水分含量是一个重要参数,因为较高的水分活度会加剧脂质氧化。此外,在较高水分水平下,壁材材料从玻璃态转变为无定形态橡胶态,分子流动性增加,导致贮藏期间包埋油脂的释放(Velasco, Dobarganes, & Marquez-Ruiz, 2003)。FOE和SOE的水分含量分别为5.91%和5.01%(表1)。SOE微胶囊中观察到的略低水分含量可归因于鼠尾草提取物赋予微胶囊壁材材料的较高疏水性。此外,提取物中多酚诱导的壁材材料有序网络促进了水分子在特定空隙中的分布,有利于干燥过程中水分的扩散。

##### 3.2.4.2 堆积密度

由于功能性和经济性原因,堆积密度是粉末产品的重要性质。较高的堆积密度有利于降低运输和包装成本,而过低的堆积密度会影响粉末的其他性质,如流动性。FOE和SOE微胶囊的堆积密度分别为0.39 g/ml和0.42 g/ml(表1),高于文献中报道的使用脱脂奶粉包埋的鱼油数值(Aghbashlo, Mobli, Madadlou, & Rafiee, 2013)。微胶囊堆积密度的差异可能与微胶囊形貌的差异有关,如球形度和表面规则性。球形且表面规则、无凹陷或皱纹的颗粒可在给定体积内更紧密地堆积,从而产生更高的堆积密度。因此,在本研究中,SOE较高的堆积密度证实了与FOE相比,SOE形成了更光滑、更规则的微胶囊。此外,SOE较高的堆积密度还表明,与FOE粉末相比,SOE粉末对氧化降解具有更好的稳定性。堆积密度越高,微胶囊内存在的夹带空气越少,因此核心油相氧化劣变的可能性越低。

##### 3.2.4.3 吸湿性

喷雾干燥颗粒易从周围环境中吸收水分,在贮藏过程中产生粘性和结块现象,除非采取必要的预防措施。在两种微胶囊中,FOE的吸湿性值低于SOE(表1)。这可能是由于FOE的表面油含量高于SOE。颗粒表面存在的未包埋油脂形成疏水层,从而减少了微胶囊对水分的吸收。

##### 3.2.4.4 色泽

氧化过程中非挥发性分解产物(如氧化甘油三酯和游离脂肪酸)的积累可导致色泽变化,这反映了高脂食品中油脂劣变的程度。新鲜包埋的FOE呈略带灰白色,主要由呈浅棕色的阿拉伯胶赋予。同样,新鲜包埋的SOE由于含有原本呈浅黄绿色的鼠尾草提取物而颜色略深。在加速贮藏研究的不同天数中,FOE和SOE的色泽参数存在明显差异(表1)。两种包埋样品在贮藏期间L*值均呈下降趋势,但在60°C加速贮藏研究全过程中,SOE的下降幅度始终小于FOE。

色度参数a*和b*值在贮藏期间均发生显著变化。两种新鲜包埋粉末均显示正值a*,表示接近红色色度,FOE样品的值显著更高。含脂配方红色度的增加表明存在油脂氧化产物。所有样品的b*值均为正值,表示黄色色度,其强度在贮藏期间增加。FOE在贮藏期间表现出的较高黄度值表明表面油快速氧化,产生了有色次级和三级氧化产物。

#### 3.2.5. 微胶囊在缓冲盐溶液中的体外释放模式

微胶囊在含酒精的缓冲盐溶液中的体外释放模式模拟了微胶囊掺入食品系统后的命运,尤其是当食品中含有非极性组分(如油脂乳液)或蛋白质沉淀剂(如发酵产品中的酒精)时。SOE在缓冲盐溶液中显示出恒定的油脂释放速率,每小时取样中油脂释放量均小于5%,而FOE在孵育第一小时后为11-14%(图4),表明SOE形成了能够更好地保护微胶囊免受表面崩解和油脂向食品系统中扩散的壁材基质。4 h孵育期间的累积油脂释放量在FOE中占总油的55.22%,而在SOE中为19.74%。由于FOE的表面油含量与缓冲盐溶液中的累积油脂含量之间存在巨大差异,FOE中显著较高的油脂释放速率可能主要与FOE微胶囊的结构完整性较差有关,导致油脂快速扩散到介质中。相反,在SOE中,交联降低了聚合物结构的移动性,增强了其耐水性。两种微胶囊在最初1 h内均表现出最大油脂释放速率,随后呈线性释放模式。这些结果与从SEM和AFM图像获得的结构推断一致。

#### 3.2.6. 微胶囊的体外胃肠道消化特征

##### 3.2.6.1 SGF和SIF对油脂释放的影响

为了评估微胶囊化鱼油口服递送或将生物活性物质靶向递送至胃肠道(GIT)特定部位的功效,在进行体内试验之前,有必要在体外测试微胶囊在胃肠道转运过程中的稳定性和释放行为(Kosaraju et al., 2006)。此外,蛋白质-多酚相互作用也可能影响蛋白质被胃肠道酶的消化。暴露于模拟胃液后释放的油脂量,FOE和SOE样品分别为总油的71.71%和64.26%(表1)。微胶囊中油脂的释放主要取决于壁材基质被胃液中的酸和酶表面崩解的程度。FOE中释放的较高油脂量可能归因于存在相对较多的破损胶囊,使酶易于接触并加速胶囊降解。出于同样原因,SOE微胶囊中形成的强聚合物基质即使在胃液中也延缓了微胶囊中油脂的释放。进一步暴露于模拟肠液后,FOE和SOE分别释放了总油的15.41%和14.98%(表1)。显然,酪蛋白在含蛋白酶胃蛋白酶的低pH胃液环境中可能发生了结构重排,释放出大部分油脂。然而,被困在崩解/部分消化聚合物网络中的油脂预计会在肠道中通过胰酶的作用进一步释放,胰酶含有降解阿拉伯胶的淀粉酶和降解酪蛋白的蛋白酶。需要体内人体临床研究来了解任何设计配方中油脂的实际生物利用度。此外,预计在一定程度上,结肠液以及通常栖息在结肠中的细菌也会导致油脂释放。在本研究中,由于微胶囊中负载的80%以上油脂已在胃肠道中释放,因此未研究微胶囊在结肠中的释放。此外,结肠是胃肠道中最难在实验室模拟的部分,因为细菌种群存在很大差异,且需要在厌氧条件下培养结肠细菌。因此,许多研究者更倾向于直接在动物模型上进行测试(McClements, 2014)。

##### 3.2.6.2 胃肠道消化物的显微分析

使用倒置显微镜观察消化前后的微胶囊,以确认关于微胶囊在胃肠道中命运的推断。两种微胶囊在模拟消化液中消化前均显示出聚集和絮凝物形成(图5 A和D)。体外消化后,两种微胶囊的结构均被破坏。经过胃相后,由于酪蛋白-阿拉伯胶复合物的水解和静电排斥的减弱,观察到液滴尺寸减小(图5 B和E)。消化特征显示,与SOE(图5 E)相比,FOE(图5 B)在胃液中形成聚集体的速率较低,表明FOE中胶囊的剧烈破裂。然而,随着消化进入肠相,两种消化物的外观大致相似(图5 C和F)。结果表明,包埋在交联微球中的鱼油将被消化,其消化方式大致类似于常规鱼油微胶囊。

#### 3.2.7. 微胶囊中脂质氧化的测定

##### 3.2.7.1 PV的测定

为了确定鼠尾草提取物对脂肪氧化的保护作用,将微胶囊的氧化模式与用于包埋的纯鱼油(PFO)和含1%鼠尾草提取物的鱼油(SFO)进行了比较。我们之前的报道中已报道了鼠尾草提取物在标准抗氧化体外测定中的保护作用(Binsi et al., 2016)。纯鱼油的PV为4.56 mEq O₂/kg油,在FOE和SOE中分别大幅增加至10.89和12.32 mEq O₂/kg油(图6A)。这清楚地表明,在喷雾干燥过程中,油粒在被包埋之前经历了某种程度的氧化,而添加抗氧化剂在此阶段无法提供保护。然而,包埋的保护作用在贮藏期间显而易见,因为PFO在贮藏24 h后过氧化值增加了十倍以上。SFO也遵循与PFO相似的氧化模式,但在贮藏期间显示出低于PFO的PV。FOE和SOE样品均表现出至第5天的渐进式增加,SOE在任何取样日的绝对值均较低。此前有报道,0.02%的鼠尾菜提取物在加速氧化贮藏条件下对菜籽油稳定性具有高度保护作用,与相同浓度的丁基羟基甲苯(BHT)相当(Bandoniene, Pukalskas, Venskutonis, & Gruzdien, 2000)。然而,本研究结果表明了一种物理保护机制,而非预期的多酚自由基清除活性,因为保护作用在贮藏期间比在喷雾干燥期间更为明显。从其他参数的结果可以合理推断,SOE的壁比FOE更致密、更具保护性,除了提供从表面到核心的氧屏障特性外,还防止了核心油脂进一步扩散到表面。

##### 3.2.7.2 硫代巴比妥酸反应物(TBARS)的测定

在加速贮藏条件下,纯鱼油和包埋样品的TBARS值存在显著差异(p < 0.05)(图6B)。两种包埋物呈现可比较的初始TBARS值,FOE为1.03,SOE为0.92,而PFO和SFO的值显著较低(p < 0.05)。乳液的均质化涉及强烈的机械应力和湍流,在喷雾干燥过程中进一步暴露于高温会导致油脂快速氧化。所有样品的TBARS值在贮藏24 h后均超过2的限值,并且在贮藏前两天显示几乎相似的值。所有样品显示的初始高值可能与样品中已存在的过氧化物生成次级氧化产物有关。然而,在进一步贮藏期间,SOE样品中TBARS值的增加速率最低,甚至低于SFO。关于抗氧化剂在喷雾干燥中的应用,Serfert, Drusch, & Schwarz(2009)推断,在液体系统中有效的抗氧化剂不一定能提高喷雾干燥包埋油脂的稳定性。然而,本研究结果表明,可以通过在油脂中添加抗氧化剂来增强保护作用,但氧化速率的差异可能与界面处形成有效的物理屏障有关。换句话说,稳定性的提高是由于酪蛋白酸钠和阿拉伯胶形成了玻璃态外壳,降低了氧的分子流动性,从而减缓了脂质氧化的速率。

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## 4. 结论

本研究的目的是通过添加富含多酚的鼠尾草提取物作为蛋白质交联剂和鱼油抗氧化剂,以提高喷雾干燥微胶囊的结构和氧化稳定性,从而最大限度地减少喷雾干燥过程中高温的影响。微胶囊的FT-IR光谱证实了多酚与壁材聚合物的相互作用。添加鼠尾草提取物改善了微胶囊的表面形貌和尺寸均匀性。通过在喷雾干燥前在乳液中添加1%水平的鼠尾草提取物,实现了更高的包埋效率和包埋产品中更低的表面油含量。加速贮藏研究中脂质氧化参数的结果表明了一种物理保护机制。尽管在体外研究中FOE样品的总油脂释放量较高,但鼠尾草提取物对脂肪氧化的保护作用以及在正常食品环境中的稳定性是显著的。因此,本研究结果表明,可在喷雾干燥前在鱼油中添加鼠尾草提取物。然而,鱼油在胃肠道中的完整释放模式尚不能令人满意地阐明。需要进一步研究以增强微胶囊在胃肠道靶向部位的释放特性。

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## 致谢

本研究在印度科学与工程研究委员会(SERB,印度科技部-印度食品加工工业部)资助的研究项目下完成。