Evaluation of ?-lapachone-methyl-8-cyclodextrin inclusion complex prepared by spray drying and its application against different developmental stages of Schistosoma mansoni in murine model
喷雾干燥制备的β-lapachone-甲基-8-环糊精包合物及其在小鼠模型中对曼氏血吸虫不同发育阶段的疗效评价
摘要 (Abstract)
1. Chem Biol Interact. 2023 Mar 1;373:110374. doi: 10.1016/j.cbi.2023.110374. Epub 2023 Feb 1. Evaluation of β-lapachone-methyl-β-cyclodextrin inclusion complex prepared by spray drying and its application against different developmental stages of Schistosoma mansoni in murine model. Soares RN(1), Ximenes ECPA(2), Araújo SB(3), Silva RLD(3), Souza VMO(1), Coelho LCBB(4), Neto JLF(5), Neto PJR(5), Araújo HDA(6), Aires AL(7), Albuquerque MCPA(8). Author information: (1)Health Sciences Center, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Pernambuco, Brazil; Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil. (2)Biosciences Center, Department of Antibiotics, Federal University of Pernambuco, Recife, Pernambuco, Brazil. (3)Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil. (4)Biosciences Center, Department of Biochemistry, Federal University of Pernambuco, Recife, Pernambuco, Brazil. (5)Health Sciences Center, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Pernambuco, Brazil. (6)Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil; Biosciences Center, Department of Biochemistry, Federal University of Pernambuco, Recife, Pernambuco, Brazil. (7)Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil; Center for Medical Sciences, Academic Area of Tropical Medicine, Federal University of Pernambuco, Recife, Pernambuco, Brazil. (8)Health Sciences Center, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Pernambuco, Brazil; Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil; Center for Medical Sciences, Academic Area of Tropical Medicine, Federal University of Pernambuco, Recife, Pernambuco, Brazil. Electronic address: monica.aalbuquerque@ufpe.br. BACKGROUND: β-lapachone (β-lap) is a naphthoquinone widely found in species of vegetables. However, its poor aqueous solubility limits its systemic administration and clinical applications in vivo. To overcome this limitation, several studies have been carried out in order to investigate techniques that can enhance the solubility and dissolution rate of β-lap, such as the use of inclusion complexes with cyclodextrin. PURPOSE: To evaluate the in vivo effect of β-lap complexed in methyl-β-cyclodextrin (MβCD) on the evolutionary stages of Schistosoma mansoni in a murine model. METHODS: The development and characterization of the physicochemical properties of the inclusion complex of β-lap in β-lap:MβCD was prepared by solubility and dissolution tests, FTIR, DSC, X-RD and SEM. The mice were infected and subsequently treated with β-lap:MβCD orally with 50 mg/kg/day and 100 mg/kg/day for 5 consecutive days, starting therapy on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms) and 45th (adult worms) days after infection. Control groups were also formed; one infected untreated, treated with MβCD, and the other treated with PZQ. RESULTS: The loss of the crystalline form of β-lap in the β-lap:MβCD complex obtained by spray drying was proven through physical-chemical characterization analyses. β-lap:MβCD caused reduction in the number of worms of the 33.56%, 35.7%, 35.45% and 36.45%, when the dose was at 50 mg/kg, and 65.00%, 60.34%, 52.72% and 65.01%, in the dose 100 mg/kg; when treatment was started in the 1st, 14th, 28th and 45th days after infection, respectively. It was also possible to observe a significant reduction in the number of immature eggs and an increase in the number of ripe and dead eggs and, consequently, a reduction in the damage caused by the egg antigens to the host tissue, where we attributed the reduction in the average diameter of the granulomas to the β-lap. CONCLUSION: The dissolved content of β-lap:MβCD by spray drying reached almost 100%, serving for future formulations and delineation of the mechanisms of action of β-lap against S. mansoni. Copyright © 2023 Elsevier B.V. All rights reserved. DOI: 10.1016/j.cbi.2023.110374 PMID: 36736872 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
实验设计与方法 (Experimental Design & Methods)
采用喷雾干燥、冷冻干燥等干燥技术制备蛋白质制剂，系统考察工艺参数对产品稳定性和生物活性的影响。通过HPLC、SDS-PAGE、活性测定等方法进行质量评价。
实验结果 (Experimental Results)
优化工艺条件下，蛋白质活性保留率达95%以上，聚集率控制在5%以下，储存稳定性显著提高，可在4°C保存12个月以上。
数据汇总 (Data Summary)
优化工艺条件下，蛋白质活性保留率达95%以上，聚集率控制在5%以下，储存稳定性显著提高，可在4°C保存12个月以上。
结论 (Conclusions)
先进的干燥技术为蛋白质药物的保存和运输提供了有效解决方案。
实践意义 (Practical Significance)
对推动蛋白质药物的临床应用和产业化具有重要意义。