Antibacterial dual-drug delivery fiber system via a multi-layered porous Poly(caprolactone)/poly lactic acid/ZIF-8 composites

A novel dual-drug delivery platform was developed by integrating porous electrospun poly(ε-caprolactone) (PCL) fibers with a poly(lactic acid) (PLA) coating and in situ-grown zeolitic imidazolate framework-8 (ZIF-8). The porous structure, induced via vapor-induced phase separation, enabled efficient levofloxacin loading, while lysozyme was embedded within the ZIF-8 shell. This multi-layered platform (PFZL) was designed to co-deliver levofloxacin and lysozyme, addressing limitations of conventional systems in terms of drug loading, release duration, and balanced dual-drug incorporation. PFZL achieved a high drug loading of 57.9 wt% with a balanced composition (57.1 % levofloxacin, 42.9 % lysozyme), surpassing typical electrospun fiber systems. In vitro release studies demonstrated an initial burst of lysozyme followed by sustained release, while levofloxacin exhibited diffusion-controlled release mediated by PLA degradation and fiber porosity, sustaining dual release for up to 28 days. Antibacterial assays against Escherichia coli and Staphylococcus epidermidis showed that PFZL exhibited the strongest inhibition zones (42 mm and 59 mm, respectively) and 99.99 % bactericidal efficiency. In vitro release studies indicated a burst release of lysozyme within the first 24 h followed by sustained release, while levofloxacin exhibited a more gradual profile driven by PLA degradation and diffusion through the porous matrix. By 672 h, the cumulative release composition stabilized at 58 % levofloxacin and 42 % lysozyme from PFZL. This dual-release profile enhanced antibacterial synergy by combining lysozyme's initial membrane-disrupting activity with levofloxacin's intracellular action. Cytotoxicity testing using L929 fibroblasts verified biocompatibility with cell viability over 94 % for 7 days. These findings highlight PFZL as a safe and effective long-term antibacterial platform with potential applications in wound healing, implant coatings, and infection-prone biomedical devices.