Formulation development and optimization of sparfloxacin-loaded solid lipid nanoparticles integrated with microneedles for the treatment of biofilm-infected wounds

SPFX-SLNs were systematically optimized using BBD-RSM for infected wounds. • Optimized SLNs showed uniform spherical morphology with a size of ∼87 nm. • SPFX-SLNs exhibited 2-fold higher antibacterial potency than the free drug. • MNs enabled efficient skin penetration for targeted SLNs delivery. • Optimized MNs achieved a 98.61% wound closure rate by Day 14. The efficient management of infected skin wounds is severely limited by the thick bacterial biofilm within the lesion, the intractable stratum corneum barrier of the perilesional skin, and the high toxicities of potent antibiotics. Sparfloxacin (SPFX) was withdrawn from the market due to its severe systemic side effects and UV-induced phototoxicity, while its severe hydrophobicity causes localized crystalline cytotoxicity upon topical application. To safely rejuvenate this potent drug, an integrated transdermal system combining photoshielding, SPFX-loaded solid lipid nanoparticles (SPFX-SLNs) with dissolving microneedles (MNs) was developed. This study primarily focuses on the systematic screening, formulation development, and optimization of SPFX-SLNs via Box-Behnken Design-Response Surface Methodology (BBD-RSM). The optimized nanocarriers exhibited a uniform size (86.85 ± 1.89 nm) and a two-fold higher antibacterial potency against Escherichia coli ( E. coli ) than free SPFX. Mechanistically, the solid lipid core locked SPFX in a safe amorphous state to preclude crystal-induced irritation, while functioning as a physical photoshield against UV activation. By depositing the nanomedicine exclusively into infected dermis, the MN platform minimized systemic drug exposure. In a rat model of E. coli -infected biofilm wounds, the formulated SPFX-SLNs MNs achieved over 50% (58.44%) wound closure within 3 days and near-complete re-epithelialization by day 11, and a 98.61% final closure rate by day 14. Ultimately, this work establishes a comprehensive formulation development strategy for a safety-enhanced, biofilm-penetrable nanomedicine-MN hybrid that successfully repurposes a clinically restricted antibiotic for advanced wound regeneration. Download: Download high-res image (242KB) Download: Download full-size image