Biodegradable polymer microparticles are promising delivery depots for protein therapeutics due to their relatively simple fabrication and facile administration. Double-wall microspheres (DWMS) comprising a core and shell made of two distinct polymers may provide enhanced control of the drug release profiles. Using precision particle fabrication (PPF) technology, monodisperse DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL) shell of uniform thickness. Monolithic single-wall microspheres were also fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and dichloromethane as shell- and core-phase solvents, respectively, BSA was encapsulated selectively in the core region within DWMS with higher loading and encapsulation efficiency compared to using dichloromethane as core and shell solvents. BSA in vitro release rates were retarded by the presence of the drug-free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing BSA release rate. With a 14-μm thick PDLL shell, an extended period of constant-rate release was achieved.

译文

:可生物降解的聚合物微粒由于其相对简单的制造和便捷的给药方法,是用于蛋白质治疗的有前途的储库。包含由两种截然不同的聚合物制成的核和壳的双壁微球(DWMS)可以增强对药物释放曲线的控制。使用精密颗粒制造(PPF)技术,以负载模型蛋白牛血清白蛋白(BSA)的聚(丙交酯-乙交酯)(PLG)核心和不含药物的聚(d,l-乳酸)制成单分散DWMS( PDLL)厚度均匀的外壳。还制造了整体式单壁微球,以模拟负载BSA的PLG核心。分别使用乙酸乙酯和二氯甲烷作为壳层和核心相溶剂,与使用二氯甲烷作为核心和壳层溶剂相比,BSA被选择性地封装在DWMS的核心区域中,具有更高的负载和封装效率。无药物的PDLL壳的存在阻碍了BSA的体外释放速率。此外,增加PDLL外壳厚度会导致BSA释放速率降低。使用14μm厚的PDLL外壳,可以实现延长的恒定速率释放。

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