Kim Yuyoung, Sah Hongkee
College of Pharmacy, Ewha Womans University, 52 Ewhayeodaegil, Seodaemun-gu, Seoul 03760, Korea.
Pharmaceutical Product Research Laboratories, Dong-A ST R&D Center, 21, Geumhwa-ro 105beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do 17073, Korea.
Pharmaceutics. 2021 Jan 21;13(2):137. doi: 10.3390/pharmaceutics13020137.
A self-healing microencapsulation process involves mixing preformed porous microspheres in an aqueous solution containing the desired protein and converting them into closed-pore microspheres. Spongelike poly-d,l-lactide--glycolide (PLGA) microspheres are expected to be advantageous to protein loading through self-healing. This study aimed to identify and assess relevant critical parameters, using lysozyme as a model protein. Several parameters governed lysozyme loading. The pore characteristics (open-pore, closed-pore, and porosity) of the preformed microspheres substantially affected lysozyme loading efficiency. The type of surfactant present in the aqueous medium also influenced lysozyme loading efficiency. For instance, cetyltrimethylammonium bromide showing a superior wetting functionality increased the extent of lysozyme loading more than twice as compared to Tween 80. Dried preformed microspheres were commonly used before, but our study found that wet microspheres obtained at the end of the microsphere manufacturing process displayed significant advantages in lysozyme loading. Not only could an incubation time for hydrating the microspheres be shortened dramatically, but also a much more considerable amount of lysozyme was encapsulated. Interestingly, the degree of microsphere hydration determined the microstructure and morphology of closed-pore microspheres after self-healing. Understanding these critical process parameters would help tailor protein loading into spongelike PLGA microspheres in a bespoke manner.
一种自修复微囊化过程包括将预先形成的多孔微球在含有所需蛋白质的水溶液中混合，并将它们转化为闭孔微球。海绵状聚-d，l-丙交酯-乙交酯（PLGA）微球有望通过自修复在蛋白质负载方面具有优势。本研究旨在以溶菌酶作为模型蛋白来识别和评估相关关键参数。有几个参数控制着溶菌酶的负载。预先形成的微球的孔特征（开孔、闭孔和孔隙率）对溶菌酶负载效率有显著影响。水介质中存在的表面活性剂类型也会影响溶菌酶负载效率。例如，具有优异润湿功能的十六烷基三甲基溴化铵比吐温80使溶菌酶负载程度增加了两倍多。以前通常使用干燥的预先形成的微球，但我们的研究发现，在微球制造过程结束时获得的湿微球在溶菌酶负载方面显示出显著优势。不仅可以大大缩短微球水合的孵育时间，而且可以包封更多量的溶菌酶。有趣的是，微球水合程度决定了自修复后闭孔微球的微观结构和形态。了解这些关键工艺参数将有助于以定制方式将蛋白质负载到海绵状PLGA微球中。
