Institute of Pharmaceutical Technology and Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt am Main, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Saarland University, Saarbruecken, Germany.
Institute of Pharmaceutical Technology and Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt am Main, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Saarland University, Saarbruecken, Germany.
Eur J Pharm Sci. 2018 Nov 1;124:71-79. doi: 10.1016/j.ejps.2018.08.028. Epub 2018 Aug 24.
Poly(lactide-co-glycolide) (PLGA) has been widely investigated for fabricating electrospun fibers due to their biocompatibility, paired with the capacity for encapsulating different drugs. However, such scaffolds shrink and distort upon contact with biological media, which is undesired for local drug application. To address this issue, we fabricated composite fiber scaffolds with the combination of PLGA and poly(ethylene glycol) (PEG). Scaffold shrinkage could successfully be overcome, however, the release kinetics of the encapsulated drug was strongly dependent on the amount of PEG. The addition of 5% PEG resulted in slower drug release due to a significant increase in fiber diameters. In contrast, the drug release rate was accelerated for fibers containing 10% PEG due to the water-soluble nature of the polymer. Furthermore, co-delivery of two different drugs, the small molecule acyclovir and the model protein bovine serum albumin was realized by two different approaches, coaxial electrospinning and immobilization of the drugs on the surface of the fibers, and drug release was found to be strongly dependent on the loading procedure. Based on our findings, key factors for understanding and controlling physicochemical properties of PLGA/PEG composite fibers as well as tuning drug release could be identified, providing an essential basis for rational design of electrospun fiber-based drug carriers.
聚（乳酸-共-乙醇酸）（PLGA）由于其生物相容性，能够包裹不同的药物，因此被广泛用于制造电纺纤维。然而，此类支架在与生物介质接触时会收缩和变形，这对于局部药物应用是不理想的。为了解决这个问题，我们将 PLGA 和聚乙二醇（PEG）结合在一起制造了复合纤维支架。成功地克服了支架收缩的问题，但是包裹药物的释放动力学强烈依赖于 PEG 的含量。添加 5%PEG 会由于纤维直径的显著增加而导致药物释放速度变慢。相比之下，由于聚合物的水溶性，含有 10%PEG 的纤维的药物释放速度加快。此外，通过两种不同的方法，即同轴电纺和药物固定在纤维表面上，实现了两种不同药物，即小分子阿昔洛韦和模型蛋白牛血清白蛋白的共递送，并且发现药物释放强烈依赖于装载程序。基于我们的发现，可以确定理解和控制 PLGA/PEG 复合纤维的物理化学性质以及调节药物释放的关键因素，为基于电纺纤维的药物载体的合理设计提供了重要基础。
