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.
Objective: This study aimed to develop and characterize the physicochemical properties of a self-emulsion drug delivery system (SNEDDS) incorporating galangal extract (GE) and lemongrass oil (LGO). Then, to develop mouthwash powders containing GE- and LGO-loaded SNEDDS (GL-mouthwash powder) as a promising alternative for preventing and treating denture stomatitis. Methods: The solubility of GE in various vehicles was determined. Subsequently, pseudo-ternary phase diagrams of the different ingredients, oil (LGO), surfactant (Tween® 80), and co-surfactant (Propylene glycol) were selected to develop the SNEDDS. Then, SNEDDS containing GE and LGO (GL-SNEDDS) were prepared and characterized. The optimized liquid GL-SNEDDS was transformed into GL-mouthwash powder by absorbing onto mannitol and blending with a sweetener. Subsequently, various evaluations including drug recovery, moisture content, emulsification time, stability, anti-Candida activity, and in vitro cytotoxicity were performed. Results: The developed SNEDDS formulation improved GE and LGO solubility. The optimized GL-SNEDDS exhibited a small droplet size of 148.2 ± 2.1 nm with a polydispersity index of 0.11 ± 0.03 and a zeta potential of 2.14 ± 0.11 mV. In addition, the GL-mouthwash powder demonstrated a high drug recovery of >80% with a low moisture of <10% and exhibited greater physicochemical stability under accelerated conditions. The developed GL-mouthwash powder rapidly formed a stable nanoemulsion within 2 min after reconstitution. Interestingly, GL-mouthwash powder exhibited strong anti-Candida activity with no toxicity to human fibroblast cells, which demonstrated superior biocompatibility relative to existing commercial products. Conclusions: These findings suggest that GL-mouthwash powder has potential as an alternative prevention and treatment of oral Candida infection.