Electrospun PLA/PCL Membranes for Sustained Transdermal Rifampicin Delivery: Biocompatibility, Stability, and Antimycobacterial Activity
Poor adherence to prolonged antibiotic regimens remains a major challenge in the treatment and prevention of chronic infectious diseases such as tuberculosis. Transdermal drug delivery systems capable of sustained antibiotic release may improve therapeutic compliance while reducing the need for frequent oral administration. In this study, electrospun polymeric membranes based on poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were developed as transdermal rifampicin delivery platforms. Homogeneous nanofibrous membranes with average fiber diameters of approximately 250 nm were successfully fabricated and exhibited efficient drug incorporation while preserving the structural integrity of the polymeric matrix. The electrospun membranes retained sufficient tensile strength and dimensional stability after accelerated temperature–humidity aging, supporting their stability during storage, handling, and application. In vitro cytotoxicity and biocompatibility assays using primary human peripheral blood mononuclear cells (PBMCs) demonstrated that the developed systems did not induce significant cytotoxic or pro-inflammatory responses. Transdermal permeation studies using an in vitro mouse skin model demonstrated sustained rifampicin diffusion for at least 72 h. Importantly, the antibiotic recovered after skin permeation preserved antimycobacterial activity against Mycobacterium tuberculosis H37Ra and Mycobacterium bovis BCG, confirming that rifampicin maintained its biological functionality after electrospinning and transdermal migration. Overall, these findings demonstrate the potential of electrospun PLA/PCL membranes as stable and biocompatible transdermal antibiotic delivery systems capable of sustained release and preservation of antimicrobial activity. This proof-of-concept study supports the translational potential of electrospun polymeric platforms for controlled antibiotic delivery in long-term infectious disease therapies.