Department of Molecular Pharmacology, Physiology, and Biotechnology, Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA.
Acta Biomater. 2013 Jan;9(1):4569-78. doi: 10.1016/j.actbio.2012.08.005. Epub 2012 Aug 16.
Wet spun microfibers have great potential for the design of multifunctional controlled release scaffolds. Understanding aspects of drug delivery and mechanical strength, specific to protein molecular weight, may aid in the optimization and development of wet spun fiber platforms. This study investigated the intrinsic material properties and release kinetics of poly(l-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA) wet spun microfibers encapsulating proteins with varying molecular weights. A cryogenic emulsion technique developed in our laboratory was used to encapsulate insulin (5.8 kDa), lysozyme (14.3 kDa) and bovine serum albumin (BSA, 66.0 kDa) within wet spun microfibers (~100 μm). Protein loading was found to significantly influence mechanical strength and drug release kinetics of PLGA and PLLA microfibers in a molecular-weight-dependent manner. BSA encapsulation resulted in the most significant decrease in strength and ductility for both PLGA and PLLA microfibers. Interestingly, BSA-loaded PLGA microfibers had a twofold increase (8±2 MPa to 16±1 MPa) in tensile strength and a fourfold increase (3±1% to 12±6%) in elongation until failure in comparison to PLLA microfibers. PLGA and PLLA microfibers exhibited prolonged protein release up to 63 days in vitro. Further analysis with the Korsmeyer-Peppas kinetic model determined that the mechanism of protein release was dependent on Fickian diffusion. These results emphasize the critical role protein molecular weight has on the properties of wet spun filaments, highlighting the importance of designing small molecular analogues to replace growth factors with large molecular weights.
湿法纺丝微纤维在多功能控制释放支架的设计中具有巨大的潜力。了解药物输送和机械强度方面的特性，特别是针对蛋白质分子量的特性，可能有助于优化和开发湿法纺丝纤维平台。本研究调查了包封具有不同分子量的蛋白质的聚（L-乳酸）（PLLA）和聚（乳酸-共-乙醇酸）（PLGA）湿法纺丝微纤维的固有材料特性和释放动力学。我们实验室开发的低温乳液技术用于将胰岛素（5.8 kDa）、溶菌酶（14.3 kDa）和牛血清白蛋白（BSA，66.0 kDa）包封在湿法纺丝微纤维中（~100 μm）。研究发现，蛋白质负载以分子量依赖的方式显著影响 PLGA 和 PLLA 微纤维的机械强度和药物释放动力学。BSA 包封导致 PLGA 和 PLLA 微纤维的强度和延展性显著降低。有趣的是，与 PLLA 微纤维相比，载有 BSA 的 PLGA 微纤维的拉伸强度增加了两倍（从 8±2 MPa 增加到 16±1 MPa），断裂伸长率增加了四倍（从 3±1%增加到 12±6%）。PLGA 和 PLLA 微纤维在体外的蛋白质释放时间长达 63 天。通过 Korsmeyer-Peppas 动力学模型的进一步分析确定，蛋白质释放的机制取决于菲克扩散。这些结果强调了蛋白质分子量对湿法纺丝纤维性能的关键作用，突出了设计小分子类似物以替代具有大分子量的生长因子的重要性。
