School of Medicine, Southeast University, Nanjing, China; Lab for Trauma and Surgical Infections, Department of Surgery, Jinling Hospital, Nanjing, China.
School of Medicine, Nanjing University, Nanjing, China.
Mater Sci Eng C Mater Biol Appl. 2018 Aug 1;89:213-222. doi: 10.1016/j.msec.2018.04.009. Epub 2018 Apr 11.
Treatment of non-healing infected wounds is an arduous task in clinical practice. Early antibacterial strategy and subsequent promotion of granulation tissue growth facilitate to cure the wounds. For this purpose, we fabricated a sequential drug delivery system by incorporation of an injectable hydrogel with porous PLGA microspheres. Vancomycin was linked to the injectable hydrogel via the reversible Schiff's base reaction, and VEGF were encapsulated into PLGA microspheres. After adding vancomycin, the strength and elasticity of the hydrogel were improved, and the gelation time was shortened. The results also demonstrated that the releasing profile of vancomycin was pH-dependent and the VEGF's profile was adjustable by changing the pore sizes of PLGA microspheres. The duration of VEGF release was longer than vancomycin. This hybrid system was valid to inhibit bacteria growth and accelerate vein endothelial cell proliferation in vitro. In rat models, it was effective to manage non-healing infected wounds by reducing inflammation and promoting angiogenesis. In conclusion, this sequential delivery system is promoting to manage non-healing infected wounds, and also provides a new thought to realize the staged drug release.
治疗难愈性感染创面是临床实践中的一项艰巨任务。早期的抗菌策略和随后促进肉芽组织生长有助于治愈创面。为此，我们通过将可注射水凝胶与多孔 PLGA 微球结合来构建顺序药物递送系统。万古霉素通过可逆希夫碱反应与可注射水凝胶连接，并且 VEGF 被包封到 PLGA 微球中。加入万古霉素后，水凝胶的强度和弹性得到改善，凝胶时间缩短。结果还表明，万古霉素的释放曲线与 pH 值有关，并且通过改变 PLGA 微球的孔径可以调节 VEGF 的释放曲线。VEGF 的释放持续时间长于万古霉素。该混合系统可有效抑制细菌生长并促进体外静脉内皮细胞增殖。在大鼠模型中，通过减少炎症和促进血管生成，该系统可有效治疗难愈性感染创面。总之，该递药系统有利于治疗难愈性感染创面，并为实现阶段性药物释放提供了新的思路。
