RESUMEN
Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using ß-cyclodextrin (ß-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the ß-CD was -5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using ß-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.
RESUMEN
Vulvovaginal candidiasis (VVC) is a vaginal infection caused by abnormal growth of Candida sp., especially Candida albicans, in the vaginal mucosa. A shift in vaginal microbiota is prominent in VVC. The presence of Lactobacillus plays a vital role in maintaining vaginal health. However, several studies have reported resistance of Candida sp. against azoles drugs, which is recommended as VVC treatment. The use of L. plantarum as a probiotic would be an alternative to treat VVC. In order to exert their therapeutic activity, the probiotics needed to remain viable. Multilayer double emulsion was formulated to obtain L. plantarum loaded microcapsules (MCs), thus improving its viability. Furthermore, a vaginal drug delivery system using dissolving microneedles (DMNs) for VVC treatment was developed for the first time. These DMNs showed sufficient mechanical and insertion properties, dissolved rapidly upon insertion, facilitating probiotic release. All formulations proved non-irritating, non-toxic, and safe to apply on the vaginal mucosa. Essentially, the DMNs could inhibit the growth of Candida albicans up to 3-fold than hydrogel and patch dosage forms in ex vivo infection model. Therefore, this study successfully developed the formulation of L. plantarum-loaded MCs with multilayer double emulsion and its combination in DMNs for vaginal delivery to treat VVC.