DEVELOPMENT OF AN INNOVATIVE VAGINAL FILM DOSAGE FORM FOR THE COMBINED DELIVERY OF PROBIOTICS AND AN ANTIBIOTIC

Bacterial vaginosis (BV) is one of the most common vaginal infections among women of reproductive age. While antibiotics are the standard treatment for BV, many women experience high recurrence rates with antibiotic therapy alone. This is because antibiotics cannot rebuild a healthy Lactobacillus-dominated vaginal microbiome. Consequently, women often take probiotics to restore a healthy vaginal microbiome. To provide more effective treatment for BV, products that can deliver probiotics and antibiotics simultaneously are needed. Design of products which are portable, affordable, self-administered, and discreet to use will enhance user acceptability. The work presented here focuses on developing a novel vaginal film platform for the codelivery of probiotics and antibiotics using layer-by-layer casting technology. Specifically, extended release of probiotics was achieved by incorporating the functional polymer Eudragit RS PO and optimizing the manufacturing process to preserve probiotic viability. Vaginal films have demonstrated flexibility and the ability to preserve probiotic viability while delivering probiotics and antibiotics simultaneously. Briefly, in this work, we found that: 1) Trehalose is effective in preserving Lactobacillus viability using both spray drying and freeze-drying methods, achieving a survival rate greater than 90%. Spray drying has higher encapsulation efficiency compared to freeze drying. 2) Water-based solvent casting can preserve probiotics by using pullulan and trehalose as protective agents. In contrast, acetone-based solvent casting can damage probiotic viability due to exposure to organic solvents. Similarly, hot melt extrusion damages probiotic viability due to high temperature and shear rate. 3) Vaginal films can achieve the codelivery of antibiotics and probiotics using layer-by-layer casting. Eudragit RSPO was used as the functional polymer to achieve extended release of probiotics. 4) 3D printing can manufacture flexible, soft, and safe metronidazole vaginal films. Collectively, this project: 1) Identified protective agents that can preserve probiotic viability after drying 2) Demonstrated that using functional polymers can achieve extended release for probiotics. 3) Explored the potential of using vaginal films to deliver probiotics and antibiotics simultaneously.