Development of bifunctional vaginal suppositories by joint use terconazole and probiotic for treatment and prophylaxis of vulvovaginal candidiasis

The objective of this article is the creation and investigation of bifunctional suppositories that are endowed with antifungal and probiotic properties intended for the treatment of vulvovaginal candidiasis (VVC) and colonization of the vaginal cavity by powerful lactobacilli.Freeze-dried Lactobacillus delbrueckii MH10 was used as a probiotic, which is an active producer of H2O2 isolated from a healthy woman's vagina. Hydrophilic PEG 4000/400, amphiphilic Suppocire AP, and lipophilic Novata ABPH bases were used for the preparation of vaginal suppositories and each included 80 mg terconazole and 25 mg (∼109 CFU) lactobacilli. The release kinetic of active agents from suppositories was studied using the British Pharmacopeia's basket dissolution method, and the physicochemical properties were studied using known methods. Bioadhesion of suppositories was evaluated by flow rate from polyacrylamide substrate inclined at 60°. Antagonism of lactobacillus against fungi was studied using the disk diffusion method and joint cultivation in simulated vaginal fluid.The release rate of active ingredients from the suppositories was PEG 4000/400 > Suppocire AP > Novata ABPH in decreasing order. Suppositories made of Suppocire AP possessed higher adhesion ability to artificial mucosa and longer shelf life. It was revealed that during joint cultivation L. delbrueckii MH10 kills more than 90% of C. albicans population.Due to its physicochemical, biopharmaceutical, and bioadhesive properties, the base Suppocire AP is preferable for manufacturing vaginal bifunctional suppositories. Lactobacilli kill C. albicans by coaggregating and direct releasing hydrogen peroxide onto target cells.