Glassy Surfactants Enable Ultra-High Concentration Biologic Therapeutics
玻璃状表面活性剂实现超高浓度生物治疗药物
摘要 (Abstract)
<jats:title>Abstract</jats:title> <jats:p>Protein therapeutics, like peptides and antibodies, have become critical to healthcare. Despite their exceptional potency and specificity, biopharmaceuticals are prone to aggregation, often necessitating low formulation concentrations as well as cold storage and distribution to maintain stability. Yet, high doses are required to treat many diseases. To achieve these doses, most approved protein drug products are administered intravenously, imposing excessive burdens on patients and the healthcare system. New approaches are needed to formulate proteins at high concentrations to enable less burdensome subcutaneous injection, preferably in an autoinjector format. To address this challenge, we report a subcutaneously injectable biotherapeutic delivery platform composed of spray-dried protein microparticles suspended in a non-solvent liquid carrier. These microparticles contain only active biopharmaceutical agent and a high glass transition temperature polyacrylamide-derived copolymer excipient affording several key benefits over traditional excipients, including: (i) improved stabilization of biopharmaceuticals through the spray drying process, and (ii) improved morphology and properties of the spray-dried particles, enhancing suspension injectability. Experiments with albumin and antibodies demonstrate that this technology enables ultra-high-concentration protein formulations (exceeding 500 mg/mL) that are injectable through standard needles with clinically relevant injection forces. Additionally, experiments in mice with two clinically relevant antibody drugs show these ultra-high- concentration formulations reduce required injection volumes without altering pharmacokinetics or efficacy. This approach could nearly triple the number of commercial protein drugs amenable to subcutaneous administration, dramatically reducing burden and improving access to these critical biopharmaceuticals.</jats:p> <jats:sec> <jats:title>One Sentence Summary</jats:title> <jats:p>Here we leverage a unique copolymer excipient to enable ultra-high concentration protein formulations with improved stability and amenable to subcutaneous injection that can reduce patient burden, lower costs, and improve access to critical drugs.</jats:p> </jats:sec>
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。