3D printed reservoir-like vaginal rings for antibiotic delivery

Abstract

Targeting the development of 3D printed reservoir-like vaginal rings (VRs) intended to fulfill the needs of precision medicine, prototypes ensuring prolonged release of metronidazole (MTZ) were preliminary manufactured and tested. Indeed, this drug represents the first-line therapy against bacterial vaginosis, which would especially benefit from convenient as well as easy dose adjustment and from more than 48 h continuous release, thus avoiding barely tolerated and repeated administrations.

Starting from a soft thermoplastic elastomer (TPE), hollow ring structures were successfully printed at 190 °C and then extemporaneously filled with drug-loaded, in-situ-crosslinking hydrogel formulations based on alginate (ALG). 3 VR designs, differing in dimensions, number of open surfaces as well as in relevant areas were investigated, together with 9 drug-saturated hydrogel formulations containing extra suspended MTZ particles (20–50 %) and increasing ALG concentrations (2–6 %). Manufacturing of final rings was fine-tuned based on materials thermo-mechanical properties.

For comparison purposes, hydrogels with analogous composition were either cast using purposely developed molds or 3D printed mimicking the ring design. VR release performance turned out dependent on the drug solubility and on the surface area available for hydrogel contact with vaginal fluids. Interestingly, this surface resulted correlated to both the outer and inner structure of the system. The data collected would provide an effective asset to increase the versatility of reservoir-like VRs, making them a powerful tool towards therapy customization.

Materials

Thermoplastic elastomer (TPE; HTM8510/408 THERMOLAST® M, Shore hardness = 35, KRAIBURG TPE, D); Metronidazole (MTZ; Mw = 171.15 g/mol, nominal true density = 1.45 g/mL, d50 = 38 μm and d90 = 146 μm, Methapharmaceutical, ES); Sodium alginate (ALG; average Mw = 120000–190000 g/mol, M/G ratio = 1.56, Sigma Aldrich, D); Calcium carbonate (CaCO3; Sigma Aldrich, D); glucono-δ-lactone (GDL; Sigma Aldrich, D); Vagilen suppositories 500 mg (Alfasigma, I).

Arianna Chiappa, Alice Fusari, Marco Uboldi, Paola Petrini, Alice Melocchi, Francesco Briatico Vangosa, Lucia Zema, 3D printed reservoir-like vaginal rings for antibiotic delivery, International Journal of Pharmaceutics, Volume 671, 2025, 125217, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125217.