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.

Major depressive disorder (MDD) is a prevalent psychiatric condition linked to suicide risk and public health impact. Current antidepressants often cause side effects and have delayed efficacy, driving interest in natural compounds with antioxidant properties as alternative treatments. γ-Oryzanol (GO) exhibits antioxidant, neuroprotective, and antidepressant properties that warrant investigation. However, its clinical application is restricted due to its water-insoluble properties, which lead to poor oral bioavailability. Therefore, this study aimed to develop a γ-oryzanol solid dispersion (GOSD) to improve GO water solubility. Then, its neuroprotective effects against dexamethasone-induced toxicity in SK-N-SH cells were evaluated to forge a clear link between the formulation and the function. The GOSD was successfully developed by using a solvent melting method. The developed GOSD could enhance the water solubility of GO up to 1.37 ± 0.05 mg/mL and enabled GO release under simulated intestinal conditions, indicating oral bioavailability improvement. In addition, the GOSD maintained good physical and chemical stability under a 6-month storage period at room temperature. Regarding the neuroprotective potential of the GOSD, our findings indicated that all tested concentrations were nontoxic to SK-N-SH cells. Interestingly, through the enhanced water solubility of GO, GOSD pretreatment demonstrated superior neuroprotective efficacy over free GO against dexamethasone-induced cytotoxicity. GOSD pretreatment prior to dexamethasone exposure significantly decreased abnormal and apoptotic cells by reducing ROS levels and increasing the SOD activity. Remarkably, GOSD pretreatment restored synaptic plasticity through multiple mechanisms: reducing MAO activity, suppressing GR expression, and upregulating synaptophysin expression. These results strongly support the GOSD as a safe and effective alternative therapeutic approach for treating depressive disorders.