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The poor solubility of itraconazole (ITZ) has limited its efficacy in the treatment of vaginal candidiasis. Accordingly, the improvement of ITZ solubility using a solid dispersion technique was important to enhance its antifungal activity. Besides, as the purpose of this research was to develop local-targeting formulations, bioadhesivethermosensitive in situ vaginal gel combined with the gel-flake system was found to be the most suitable choice. To obtain optimum solubility, entrapment efficiency, and drug-loading capacity, optimization of solid dispersion (SD) and gel-flake formulations of ITZ was performed using a composite central design. The results showed that the optimized formulation of SD-ITZ was able to significantly enhance its solubility in both water and simulated vaginal fluid to reach the values of 4.211 ± 0.23 and 4.291 ± 0.21 mg/mL, respectively. Additionally, the optimized formulation of SD-ITZ gel flakes possessed desirable entrapment efficiency and drug-loading capacity. The in situ vaginal gel containing SD-ITZ gel flakes was prepared using PF-127 and PF-68, as the gelling agents, with the addition of hydroxypropyl methylcellulose (HPMC) as the mucoadhesive polymer. It was found that the obtained in situ vaginal gel provided desirable physicochemical properties and was able to retain an amount of more than 4 mg of ITZ in the vaginal tissue after 8 h. Importantly, according to the in vivo antifungal activity using infection animal models, the incorporation of the solid dispersion technique and gelflake system in the formulation of the bioadhesive-thermosensitive in situ vaginal gel led to the most significant decrease of the growth of Candida albicans reaching <1 log colony-forming units (CFU)/mL or equivalent to <10% of the total colony after 14 days, indicating the improvement of ITZ antifungal activity compared to other treated groups. Therefore, these studies confirmed a great potential to enhance the efficacy of ITZ in treating vaginal candidiasis. Following these findings, several further experiments need to be performed to ensure acceptability and usability before the research reaches the clinical stage.

Background: Marine sponges provided a great source of natural products with promising biological activity. This study was aimed to investigate the chemical constituents of methanol extracts of selected Indonesian marine sponges (Callyspongia sp., Clathria sp., Melophlus sarasinorum, and Xestospongia sp.), collected from the Saponda Islands, Southeast Sulawesi, Indonesia as well as to evaluate their antimicrobial and antioxidant activities. Methods: LCMS/MS analysis used to identify the compounds. Agar well diffusion and DPPH assays were used to evaluate the antimicrobial and antioxidant activities. Results: Chemical screening reported alkaloids, terpenoids, steroids, and saponins from all investigated sponges. The LC-MS/MS analysis identified various compounds which mainly contained steroids. Antimicrobial activity (against Bacillus subtilis, Escherichia coli, Salmonella enterica, and Candida albicans) was only shown by the Xestospongia sp. extract. Meanwhile, extracts of M. sarasinorum, Xestospongia sp., and Callyspongia sp. exhibited potent radical scavenging activity. Conclusion: The study concluded that the selected sponges could provide various groups of compounds. Methanol extracts of these sponges could be used as sources of antimicrobial and antioxidant agents.