Erythromycin-encapsulated tri-arm PCL/APTMS-Functionalized magnetic nanocomposite for targeted therapy of deep skin infections.

Antibiotic-resistant deep skin infections are a global challenge. To address this, new drug-delivery methods using advanced nanocomposites for precise, efficient, and site-specific therapy are required. In this study, Erythromycin (Ery), a macrolide-class antibiotic, has been encapsulated by a nanocomposite composed of 3-arm polycaprolactone (PCL) and 3-aminopropyltrimethoxysilane (APTMS)-functionalized magnetic iron oxide nanoparticles (MIONPs), producing Ery-PCL-APTMS/MIONPs. This nanocomposite demonstrated significant antibiofilm activity against Escherichia coli, Enterobacter sp., Pseudomonas sp., and Staphylococcus aureus, with dose- and time-dependent effectiveness and enhanced antibacterial activity at various concentrations compared with the standard drug. The sustained, time-dependent drug release exhibited an increasing release rate over time, achieving 48.35% at 56 h. In vivo assessment using an S. aureus-induced skin infection model demonstrated therapeutic efficacy, as reflected by a notable decrease in skin infection and improvements in physiological parameters, including increased body weight and normalization of hematological profiles (RBC, WBC, platelets). Histological investigation further confirmed the protective effects on the kidney and skin tissues. The physicochemical characterization using GPC and NMR (for PCl), along with FTIR, SEM, EDX, XRD, TGA, and VSM, confirmed the successful production of the Ery-PCL-APTMS/MIONPs nanocomposite, with a particle size of 14.91 nm, thermal stability, and nonmagnetic behavior. These results suggest that the Ery-encapsulated Ery-PCL-APTMS/MIONPs is a promising new nanocomposite system for localized antibiotic delivery, particularly for the treatment of deep skin infections and biomedical applications.