Mucoadhesive Hybrid System of Silk Fibroin Nanoparticles and Thermosensitive In Situ Hydrogel for Amphotericin B Delivery: A Potential Option for Fungal Keratitis Treatment

Abstract

The purpose of this work was to investigate the feasibility of a novel ophthalmic formulation of amphotericin B-encapsulated silk fibroin nanoparticles incorporated in situ hydrogel (AmB-FNPs ISG) for fungal keratitis (FK) treatment. AmB-FNPs ISG composites were successfully developed and have shown optimized physicochemical properties for ocular drug delivery. Antifungal effects against Candida albicans and in vitro ocular irritation using corneal epithelial cells were performed to evaluate the efficacy and safety of the composite formulations. The combined system of AmB-FNPs-ISG exhibited effective antifungal activity and showed significantly less toxicity to HCE cells than commercial AmB. In vitro and ex vivo mucoadhesive tests demonstrated that the combination of silk fibroin nanoparticles with in situ hydrogels could enhance the adhesion ability of the particles on the ocular surface for more than 6 h, which would increase the ocular retention time of AmB and reduce the frequency of administration during the treatment. In addition, AmB-FNP-PEG ISG showed good physical and chemical stability under storage condition for 90 days. These findings indicate that AmB-FNP-PEG ISG has a great potential and be used in mucoadhesive AmB eye drops for FK treatment.

Silk-based intelligent fibers and textiles: structures, properties, and applications

“…In addition, SF matrices have been recommended for oral, 127 transmucosal, 128 and ocular drug delivery. 129…”

Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system

“…Fibroin, an FDA-approved biomaterial generally obtained from the silk fibers of the domestic Bombyx mori silkworm through a sericin-removal degumming process, possesses excellent properties of human biocompatibility, mucoadhesiveness, non-toxicity, and preparation flexibility [ 7 , 10 – 13 ]. Therefore, fibroin has been used in a variety of drug delivery systems, including hydrogels, films, microparticles, and NP, for administrations via numerous routes of oral, parenteral, transdermal, and ophthalmic [ 8 , 14 – 19 ]. Interestingly, fibroin maintains its high stability across a broad pH range from less than 5 to 14 [ 7 ], making FNP suitable for utilizations in harsh conditions such as the gastrointestinal tract [ 20 ], the cancer microenvironment [ 21 ], and the inflammatory areas [ 22 ].…”