Electrospun PLA: Gelatin core-shell nanofibers for dual delivery of docetaxel and heparin with enhanced in vitro antiproliferative activity.

Abstract

Despite advances in chemotherapy, the clinical efficacy of docetaxel (Doc) in breast cancer treatment is limited by systemic toxicity and poor delivery efficiency. In this study, electrospun poly(lactic acid) (PLA):gelatin (Gel) core-shell nanofibers were developed as a dual drug delivery system for the co-delivery of Doc and heparin (HP). The core-shell architecture enabled the spatial compartmentalization of hydrophobic Doc within the PLA core and hydrophilic HP within the gelatin shell, allowing independent and controlled release profiles. Nanofibers containing 2, 3, and 5 wt% Doc in the core and corresponding amounts of HP in the shell were successfully fabricated. In vitro release studies performed at pH 3.0, 5.5, and 7.4 (37 °C) demonstrated a compartment-dependent release behavior, where HP exhibited rapid release (̴ 10 h), while Doc showed sustained release (̴ 80 h). These results indicate that the core-shell structure effectively regulates drug diffusion and enables distinct release kinetics for each therapeutic agent. Increased drug loading resulted in higher cumulative release for both agents. Cytotoxicity studies on MCF-7 breast cancer cells revealed that dual drug-loaded nanofibers (5 wt%, 2 mg) significantly reduced cell viability after 72 h, indicating enhanced in vitro antiproliferative activity. While Doc alone exhibited limited cytotoxic effect and HP showed negligible direct cytotoxicity, their combined delivery within the core-shell nanofiber system resulted in a markedly enhanced antiproliferative response. This enhanced effect indicates improved antiproliferative activity associated with dual-drug delivery through the core-shell nanofiber system. Overall, the developed PLA:Gel core-shell nanofibers represent a promising biomaterial-based platform for dual drug delivery of hydrophobic and hydrophilic agents, offering controlled release and promising in vitro antiproliferative activity.