Is It Possible to Perform Triple Cross-Linking of Sodium Alginate? Development of Vaginal Sponges Containing Luliconazole Based on the Alginate/Gelatin/ɛ-Poly-L-Lysine/Zinc Matrix

Background/Objectives: Vaginal administration enables optimal drug concentrations at the site of administration, but its effectiveness is limited by factors such as the vagina’s self-cleansing mechanisms and fluctuations in physiological conditions. Due to the difficulties in treating and the frequent recurrences of vaginal candidiasis, new drug formulations are required to ensure more effective therapy and sustained release of antifungal agents. Mucoadhesive vaginal sponges are a promising drug formulation providing prolonged release of the active ingredient and its contact with the vaginal mucosa. The application of polymers and their modifications plays a key role in the development of drug forms with unique and desired technological parameters. Methods: Therefore, the focus of this research was the development of a three-stage sodium alginate cross-linking technique based on polyelectrolyte complexes with gelatin and ɛ-poly-L-lysine, and additional ionic cross-linking with zinc ions, to obtain mucoadhesive vaginal sponges with an antifungal agent—luliconazole. The prepared formulations were evaluated for their pharmaceutical, mechanical, and mucoadhesive properties. In addition, antifungal and anti-biofilm action against Candida strains and compatibility with the vaginal VK2 E6/E7 epithelial cell line of the prepared sponges were assessed. Results: It was noted that the triple cross-linking process increased the mechanical properties of the developed sponges, improved mucoadhesive properties to vaginal mucosa of drug-loaded formulations, and demonstrated a sustained LUL release profile. Moreover, prepared sponges possessed improved antifungal and anti-biofilm effects against C. albicans, C. krusei, and C. parapsilosis. The prepared triple cross-linked formulations were biocompatible with the human vaginal VK2 E6/E7 epithelial cell line, depending on the exposure time and applied concentration. Conclusions: Triple cross-linked alginate sponges containing luliconazole were successfully prepared based on polyelectrolyte complexes with gelatin and ɛ-poly-L-lysine and additional ionic cross-linking with zinc ions. The triple cross-linking process of alginate improved the mechanical, mucoadhesive, and antifungal properties of the developed formulations.