Sustained dual delivery of metronidazole and viable Lactobacillus crispatus from 3D-printed silicone shells

Bacterial vaginosis (BV) is an imbalance of the vaginal microbiome in which there are limited lactobacilli and an overgrowth of anaerobic and fastidious bacteria such as Gardnerella. The propensity for BV recurrence is high, and therapies involving multiple treatment modalities are emerging to meet this need. However, current treatments requiring frequent therapeutic administration are challenging for patients and impact user compliance. Three-dimensional (3D)-printing offers a novel alternative to customize platforms to facilitate sustained therapeutic delivery to the vaginal tract. This study designed a novel vehicle intended for dual sustained delivery of both antibiotic and probiotic. 3D-printed compartmental scaffolds consisting of an antibiotic-containing silicone shell and a core containing probiotic Lactobacillus were developed with multiple formulations including biomaterials sodium alginate (SA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyethylene oxide (PEO), and kappa-carrageenan (KC). The vehicles were loaded with 50 μg of metronidazole/mg polymer and 5 × 10