Antifungal Drug Formulation for Vaginal Yeast Infection

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Johns Hopkins University
Over 138 million women worldwide are affected by recurrent yeast vaginitis or Candidiasis [1]. Candidiasis is a type of infection caused by yeast Candida albicans overgrowth, and it is one of the most common diseases affecting women. Three out of four women will have a yeast infection during their lifetime, and most women experience infection at least two times [2]. Yeast infection is often mild with symptoms including vaginal itching, pain or discomfort during urinating, redness, and swelling in the vagina. To alleviate this infection, oral doses of fluconazole and vaginal doses of miconazole in the form of a suppository are prescribed. Sulconazole is currently used as a topical antifungal treatment for skin infections. Miconazole is reported with adverse effects such as diarrhea, headache, nausea [31]. Even though there are no adverse effects of low-dose fluconazole, patients experience adverse effects when prescribing with high-dose fluconazole daily [32]. Adverse effects of sulconazole include redness, irritation, and contact dermatitis [33]. Considering that oral administrated drugs need to circulate systemically, vaginal delivery is more optimal due to dosing directly to the site of infection. On the other hand, vaginal administration would have higher efficiency in drug delivery due to its local effect on the vaginal microbiota. To formulate drugs for vaginal delivery, nanosuspension of drugs under 300 nm can help to get through mucus layer for better absorption. Antifungal drugs fluconazole, miconazole, and sulconazole were formulated in nanosuspension using various Pluronic block copolymers as stabilizers. All antifungal drugs were tested in vitro to assess potency. The effectiveness of antifungal drugs in treating vaginal C. albicans infection in mice was then tested in vivo. Antifungal drugs formulated fluconazole and sulconazole showed effectiveness in killing C. albicans both in vitro and in vivo, however, formulated miconazole only showed effectiveness in killing C. albicans in vitro. More studies are needed.
Nanosuspension, wet milling, yeast infection, C. albicans, fluconazole, miconazole, sulconazole