A potential thermosensitive poloxamer 407-based in situ hydrogel containing moxifloxacin-loaded silk fibroin nanoparticles for prolonged ocular delivery

Abstract

The aim of this study was to develop a hybrid system of thermosensitive poloxamer 407-based in situ hydrogel containing moxifloxacin-loaded silk fibroin nanoparticles (MFX-FNPs ISG) for improving the residence time of the antibacterial drug on the eye. Moxifloxacin-loaded silk fibroin nanoparticles (MFX-FNPs) were successfully formulated by absorption technique and two optimized poloxamer 407-based in situ hydrogels (ISG) were prepared by cold method. Consequently, the MFX-FNPs dispersion was embedded into these in situ hydrogels and sterilized by autoclave. Optimized MFX-FNPs displayed an average particle size of 210 nm, zeta potential of −30 mV, and moderate entrapment efficiency ∼44 %. The hybrid system of MFX-FNPs ISG possessed homogeneous solutions with acceptable osmolality, optimal pH levels, and transmittance of ∼90 % and manifested a pseudoplastic flow behavior at 35 °C. Furthermore, they exhibited a solution form at room temperature and quickly transformed into gel at ocular temperature. The in vitro release of MFX from MFX-FNPs ISG showed a prolonged drug release following Peppas-Sahlin kinetic model. Interestingly, the in vitro mucoadhesive study revealed that the combination systems significantly increased the residence time of the particles on the mucus membrane over 6 h compared to the solution and nanodispersion form. The prepared formulations showed effective antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa without causing toxicity to human corneal epithelial cells, suggesting no ocular irritation. Therefore, the MFX-FNPs ISG offer the potential to enhance the contact time of moxifloxacin on the ocular surface, thus improving the therapeutic efficacy in treating bacterial keratitis.