Different implantable electrospun meshes for simultaneous application of prednisone and doxorubicin

Abstract

Electrospinning is widely applied to prepare nanofibers that provide high specific surfaces, enhanced bioavailability of poorly water-soluble drugs, moreover, enable several administration routes such as implantation. In this perspective, biocompatible poly(vinyl alcohol) (PVA), polysuccinimide (PSI), and ε-polycaprolactone (PCL) based implantable scaffolds were developed by electrospinning to improve the bioavailability of incorporated or conjugated prednisone (Pred) and doxorubicin (Dox). Besides physicochemical characterization, the effect of the loaded amount of Prednisone on the mechanical properties of the fibers as well as their drug release profile were investigated. The drug release measurement revealed that the release profile highly depends on the polarity of the applied polymer as well as the environmental pH. Concerning electrospun meshes incorporating prednisone, the anti-inflammatory effect was monitored by measuring the release of a wide spectrum of cytokines by MDA-MB-231 cells. Besides the loading of doxorubicin, the chemical conjugation to polysuccinimide was successfully carried out which provided prolonged release as well as increased cellular uptake. Based on the different drug release profiles, poly(vinyl alcohol), polysuccinimide, and ε-polycaprolactone fibrous meshes can be used to prepare a potential multi-layered drug-containing implantable scaffold, which can provide both burst and prolonged release of prednisone and doxorubicin. The anti-inflammatory effect of prednisone could be beneficial to avoid rejection after implantation while incorporation or conjugation of doxorubicin into polysuccinimide fibers provides sufficient cytotoxicity and enhanced cellular uptake of MDA-MB-231 cells.