Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid).
Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid).
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DOI：
10.1038/s41467-022-30813-7
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发表时间：
2022-06-08
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
聚乳酸-乙醇酸共聚物（PLGA）长效释放贮库可有效延长肽类药物的作用时间。我们描述了有效的无有机溶剂的远程封装的基础上的能力，共同的uncapped PLGA结合和吸收到聚合物相净带正电荷的肽从水溶液中，在适度的温度下短时间暴露后。通过这种方法包封在低分子量PLGA 75/25微球中的亮丙瑞林在体外缓慢和连续释放肽超过56天，并以与1个月Lupron Depot®等同的方式抑制大鼠中的睾酮产生。该技术可推广到包封许多不同大小的净阳离子肽，包括奥曲肽，与传统方法相比具有竞争性的负载和包封效率。在某些情况下，远程加载的PLGA微球的体外和体内性能超过了相对于市售产品的性能。远程吸收包封进一步消除了对包封后关键的有机溶剂去除步骤的需要，从而允许在包封肽之前对无药物微球进行简单且成本有效的灭菌。生物活性肽在缓释颗粒中的包封是复杂的并且依赖于有机溶剂。在这里，作者从水中吸收聚合物相中的肽，在一类聚合物仓库中创建简单的低成本封装过程。
Poly(lactic-co-glycolic acid) (PLGA) long-acting release depots are effective for extending the duration of action of peptide drugs. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common uncapped PLGA to bind and absorb into the polymer phase net positively charged peptides from aqueous solution after short exposure at modest temperature. Leuprolide encapsulated by this approach in low-molecular-weight PLGA 75/25 microspheres slowly and continuously released peptide for over 56 days in vitro and suppressed testosterone production in rats in an equivalent manner as the 1-month Lupron Depot®. The technique is generalizable to encapsulate a number of net cationic peptides of various size, including octreotide, with competitive loading and encapsulation efficiencies to traditional methods. In certain cases, in vitro and in vivo performance of remote-loaded PLGA microspheres exceeded that relative to marketed products. Remote absorption encapsulation further removes the need for a critical organic solvent removal step after encapsulation, allowing for simple and cost-effective sterilization of the drug-free microspheres before encapsulation of the peptide. Encapsulation of bioactive peptides in slow-release particles is complex and relies on organic solvents. Here, the authors absorb peptides in a polymer phase from water, creating a simple low-cost encapsulation process in a class of polymer depot.
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