Lomefloxacin-loaded PLGA hollow nanospheres for healing MRSA-infected diabetic wound; optimization, in vitro and in vivo studies

Abstract

This study aimed to develop an efficient nano-delivery system to treat MRSA-infected diabetic wounds by continuously providing Lomefloxacin (Lome) in a constant pattern with augmented accumulation in the wound area. PLGA hollow nanospheres (PLGA-HNSs) were prepared via a single solvent emulsion evaporation method and optimized via D-optimal design where the entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and steady-state flux (Jss) were chosen as dependent variables. The optimized formula was evaluated regarding morphology, thermal analysis, and ex vivo skin permeation studies. The potentiality of the Lome-PLGA-HNS hydrogel in treating MRSA-infected diabetic wounds was assessed via in vivo studies. The optimal PLGA-HNS formula had EE% of 92.10 ± 1.5 %, PS 451.0 ± 6.3 nm, PDI 0.311 ± 0.004, ZP -28.2 ± 0.8 mV and Jss 111.45 ± 1.4 μg/cm 2 /h. The morphology assessment results confirmed the nanospheres’ hollow porous ring structure. The thermal analysis ensured the encapsulation of the drug. The ex vivo permeation study showed minor enhancement in the drug permeation across the skin, where the Jss was 2.78 ± 0.24 μg/cm 2 /h compared to 1.60 ± 0.33 μg/cm 2 /h achieved by the drug solution. However, the Lome-PLGA-HNS significantly enhanced the drug accumulation by 2.65 folds in the stratum corneum, 1.90 in the epidermis, and 4 folds in the dermis compared to the drug solution. The in vivo study displayed that Lome-PLGA–HNS–hydrogel exhibited the highest wound closure percent compared to the free drug hydrogel with 99.9 % eradication of bacterial burden after 7 days of treatment. Based on the previous findings, PLGA-HNS is a potential candidate for encapsulating and cutaneously delivering hydrophilic drugs for wound healing.