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

由于其相对简单的制造和容易的给药,可生物降解的聚合物微粒是蛋白质治疗药物的有希望的递送库。包含由两种不同聚合物制成的核和壳的双壁微球 (DWMS) 可以提供对药物释放曲线的增强控制。使用精密颗粒制造 (PPF) 技术,用模型蛋白牛血清白蛋白 (BSA) 负载的聚 (丙交酯-共-乙交酯) (PLG) 核和无药聚 (d,l-乳酸) (PDLL) 制备单分散dwm。) 壳的厚度均匀。还制造了单片单壁微球以模拟装有BSA的PLG芯。分别使用乙酸乙酯和二氯甲烷作为壳和核相溶剂,与使用二氯甲烷作为核和壳溶剂相比,BSA以更高的负载和封装效率被选择性地封装在DWMS内的核心区域中。无药物PDLL壳的存在会延迟BSA的体外释放速率。此外,增加PDLL壳厚度导致BSA释放速率降低。使用14μm厚的PDLL壳,可以延长恒定速率释放时间。

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