3D Printing Fabrication of Ethylene-Vinyl Acetate (EVA) Based Intravaginal Rings for Antifungal Therapy

Vulvovaginal candidiasis is a vaginal infection that affects women of reproductive age. Nowadays, the high administration frequency of conventional antifungal formulations, and recurrences negatively impact patients' well-being. In this context, intravaginal rings (IVRs) offer the possibility of controlled local drug delivery with one single application, thus possibly increasing patient compliance. This project aimed to fabricate 3D printed IVRs to highlight the potential application of these medical devices for antifungal therapy, as well as emphasize the employment of 3DP as alternative manufacturing tool. Ethylene-Vinyl Acetate copolymer was chosen as matrix, and the antifungal efficacy of bifonazole and clotrimazole loaded in the IVRs was compared. The resulting medical devices were characterized using Fourier Transformed Infrared spectroscopy, the thermal behavior was investigated with Thermogravimetric Analysis and Differential Scanning Calorimetry, proving the stability of the incorporated drugs. In addition, the drug release profile was evaluated in a vaginal fluid simulant pH 4.2, at 37 degrees C, showing a sustained release over a week. The compressive strength of the IVRs was investigated, confirming that the mechanical properties comply with the already commercialized devices. To evaluate the antifungal activity, an in vitro time-kill assay was performed against Candida albicans for 7 days, exhibiting a complete growth inhibition after 4 days for the 3D printed IVRs. Overall, this work represents a step forward in the production of 3D printed IVRs potentially able to exert antifungal activity with one single application.