Fu Yangmu, Du Lina, Wang Qi, Liao Weixiong, Jin Yiguang, Dong Anjie, Chen Chen, Li Zhongli
Orthopedics Department, General Hospital of Chinese PLA, Beijing, China.
Pharmazie. 2012 Apr;67(4):299-303.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a critical regulator of osteogenic capacity that is commonly used in bone grafts. The effectiveness of rhBMP-2 may be reduced as it can become unstable and degraded after injection into the body. Microspheres are considered appropriate vehicles for the sustained release of proteins in vivo. In this study, rhBMP-2 microspheres were manufactured using the water-in-oil-in-water (W/O/W) double-emulsion solvent-extraction technique by encapsulation in poly(lactic-co-glycolic) acid (PLGA). The microspheres were then embedded in two hydrogels made of either poloxamer 407 hydrogel or chitosan thioglycolic acid (CS-TA). The encapsulation efficiency and in vitro release of rhBMP-2 were examined and compared with the control release system (rhBMP-2 microspheres alone). The rhBMP-2 microspheres in the CS-TA hydrogel showed the lowest burst release (about 40% in the first 8h) among the three groups. The mechanisms may be the high viscosity of CS-TA hydrogel and the sustained release characteristics of CS-TA itself. The CS-TA hydrogel combined with PLGA microspheres can efficiently encapsulate rhBMP-2, control the burst release at early time points, and provide sustained release in vitro. It may be an appropriate rhBMP-2 vehicle for bone regeneration.
重组人骨形态发生蛋白-2（rhBMP-2）是成骨能力的关键调节因子，常用于骨移植。rhBMP-2注入体内后可能会变得不稳定并降解，从而降低其有效性。微球被认为是体内蛋白质缓释的合适载体。在本研究中，采用水包油包水（W/O/W）双乳液溶剂萃取技术，将rhBMP-2包裹于聚乳酸-羟基乙酸共聚物（PLGA）中制备微球。然后将微球包埋于由泊洛沙姆407水凝胶或壳聚糖巯基乙酸（CS-TA）制成的两种水凝胶中。检测rhBMP-2的包封率和体外释放情况，并与对照释放系统（仅rhBMP-2微球）进行比较。在三组中，CS-TA水凝胶中的rhBMP-2微球表现出最低的突释率（前8小时约为40%）。其机制可能是CS-TA水凝胶的高粘度以及CS-TA本身的缓释特性。CS-TA水凝胶与PLGA微球结合能够有效地包裹rhBMP-2，在早期时间点控制突释，并在体外提供缓释。它可能是一种适用于骨再生的rhBMP-2载体。
