Abstract

With the objective of developing a localized gentamicin sulfate (GS) delivery system with a controlled release kinetics for the prevention/management of osteomyelitis, composite electrospun fibers composed of poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) blends and GS loaded mesoporous silica nanoparticles (npSiGS) were prepared (PLA/PLGA: 1:3, 1:1, 3:1 w/w). GS was loaded into silica nanoparticles by adsorption, using a concentrated GS solution, and npSiGS were dispersed in the polymer solutions and immobilized in the polymeric matrix by occlusion, during fibers formations. For comparison, non-composite fibers with the same blend compositions containing GS simply dispersed in the polymeric phase were also produced. GS loaded nanoparticles were characterized by nitrogen adsorption/desorption isotherms and GS loading was quantified by thermogravimetric analysis. The morphology of the electrospun fibers, assessed by SEM, revealed that npSiGS were embedded along the composite fibers, some in the form of small aggregates. In vitro release studies showed that composite fibers exhibited lower initial burst releases and slower release kinetics, dependent on blend composition. Composite fibers with PLGA as the major component (25PLA-npSiGS) had the fastest release kinetics, while fibers with equal amounts of both polymers (50PLA-npSiGS) or with PLGA as the minor component (75PLA-npSiGS) had slower release kinetics, with constant GS release rates after the first day. These results suggest that PLA/PLGA blend composition can be manipulated to obtain composite fibers with a controlled and tailored GS release for at least three weeks. Finally, the antibacterial effect against Staphylococcus aureus of all produced fibers containing GS was confirmed by a disk diffusion method.

摘要

为了开发具有控制释放动力学的局部硫酸庆大霉素 (GS) 递送系统，用于预防/管理骨髓炎，由聚乳酸 (PLA) 和聚乳酸-乙醇酸共聚物组成的复合电纺纤维(PLGA) 共混物和负载 GS 的介孔二氧化硅纳米粒子 (npSiGS) 被制备 (PLA/PLGA: 1:3, 1:1, 3:1 w/w)。在纤维形成过程中，使用浓缩的 GS 溶液通过吸附将 GS 加载到二氧化硅纳米颗粒中，并且 npSiGS 分散在聚合物溶液中并通过闭塞固定在聚合物基质中。为了比较，还生产了具有相同共混组合物的非复合纤维，其中包含简单分散在聚合物相中的GS。GS负载纳米颗粒通过氮吸附/解吸等温线表征，GS负载通过热重分析定量。通过 SEM 评估的电纺纤维的形态显示 npSiGS 沿着复合纤维嵌入，其中一些以小聚集体的形式嵌入。体外释放研究表明，复合纤维表现出较低的初始爆发释放和较慢的释放动力学，这取决于共混物的组成。以 PLGA 作为主要成分 (25PLA-npSiGS) 的复合纤维具有最快的释放动力学，而具有等量两种聚合物 (50PLA-npSiGS) 或以 PLGA 作为次要成分 (75PLA-npSiGS) 的纤维具有较慢的释放动力学，具有第一天后恒定的 GS 释放率。这些结果表明，PLA/PLGA 共混组合物可以被操纵以获得具有受控和定制的 GS 释放至少三周的复合纤维。最后，通过圆盘扩散法证实了所有生产的含有GS的纤维对金黄色葡萄球菌的抗菌作用。