Advanced antibacterial wound management: comparative study of non-antibiotic drug elution and nanoparticle integration.

Wound infections affect 2% of the global population, causing chronic wounds and healthcare burdens as conventional antibiotics increasingly fail against biofilms. Consequently, attention is shifting toward advanced dressings that simultaneously prevent infection and support tissue regeneration. Among these, fibrous drug delivery systems have emerged as promising platforms for localized and controlled therapeutic delivery. Beyond platform geometry, physicochemical properties of the polymers are paramount in establishing biocompatibility, tunable degradation kinetics, and adequate mechanical integrity. PLGA and PLA/PCL-based nanofibrous platforms exhibit these favorable characteristics, even though they are still limited by issues such as limited control over release kinetics and potential instability of bioactive agents during fabrication. To address the limitations, hybrid platforms combining electrospun nanofibers with drug-loaded nanoparticles have been developed to provide structural integrity and secondary drug reservoirs for sustained release. Here, we developed a dual-carrier hybrid delivery platform to overcome burst release kinetics and achieve sustained local therapeutic levels by integrating microfluidically synthetized nanoparticles with electrospun nanofibrous matrices. To systematically elucidate the role of scaffold structure on the in-vitro performances, two delivery strategies were investigated: (i) direct entrapment of therapeutics within electrospun PLGA and PLA/PCL fibers, and (ii) surface coating of electrospun mats with PLGA nanoparticles. This study uses these approaches to encapsulate a hydrophobic agent, curcumin (CURC), a natural antimicrobial agent with limited solubility, and hydrophilic peptide, bovine lactoferricin (bLFC), which requires protection from enzymatic degradation. The use of these naturally derived compounds offers a promising non-antibiotic strategy to mitigate antibiotic resistance while promoting wound healing.