本研究的目的是表征PLGA对血管内皮生长因子（VEGF）递送复合微载体。为了减少最初的爆发释放并保护生物活性，将VEGF包裹在大豆1 -α-磷脂酰乙醇胺（PE）和1 -α-磷脂酰胆碱（PC）无水反胶束（VEGF-RM）纳米颗粒中。另外，介孔纳米六方Mg（OH）₂合成纳米结构（MNS）的PE / PC无水反胶束（MNS-RM）纳米颗粒可抑制PLGA酸性副产物引起的炎症并调节释放曲线。流动聚焦微流体几何平台用于制造PLGA复合微球（PLGA-CMP）与MNS，MNS-RM，VEGF-RM和天然VEGF的不同组合。通过体外和体内研究来研究每种制剂的基本参数，例如释放曲线，包封功效，生物活性，炎症反应和细胞毒性。结果表明，PLGA水解降解过程中产生的酸性副产物可以被缓冲，微球内部和外部的pH值在MNS降解过程中可以保持稳定。此外，通过生物活性测定证实了包封的VEGF的稳定性的显着改善。体外释放研究表明，在本发明的微载体中，VEGF的初始爆发释放已被最小化。本发明的单分散PLGA-CMP可广泛用于各种组织工程和治疗应用中.

The purpose of the present study is to characterize poly(d,l-lactide-co-glycolide) (PLGA) composite microcarriers for vascular endothelial growth factor (VEGF) delivery. To reduce the initial burst release and protect the bioactivity, VEGF is encapsulated in soybean l-α-phosphatidylethanolamine (PE) and l-α-phosphatidylcholine (PC) anhydrous reverse micelle (VEGF-RM) nanoparticles. Also, mesoporous nano-hexagonal Mg(OH)₂ nanostructure (MNS)-loaded PE/PC anhydrous reverse micelle (MNS-RM) nanoparticles are synthesized to suppress the induced inflammation of PLGA acidic byproducts and regulate the release profile. The flow-focusing microfluidic geometry platforms are used to fabricate different combinations of PLGA composite microspheres (PLGA-CMPs) with MNSs, MNS-RM, VEGF-RM, and native VEGF. The essential parameters of each formulation, such as release profiles, encapsulation efficacy, bioactivity, inflammatory response, and cytotoxicity, are investigated by in vitro and in vivo studies. The results indicate that generated acidic byproducts during the hydrolytic degradation process of PLGA can be buffered, and pH values inside and outside microspheres can remain steady during degradation by MNSs. Furthermore, the significant improvement in the stability of the encapsulated VEGF is confirmed by the bioactivity assay. In vitro release study shows that the VEGF initial burst release is well minimized in the present microcarriers. The present monodisperse PLGA-CMPs can be widely used in various tissue engineering and therapeutic applications.

https://doi.org/10.1021/acsami.0c22140

周小松