Engineering Bacteria-Responsive Intravaginal Rings for Controlled Drug Delivery

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Major advantage of implants is their ability to provide long-term drug delivery. Current intravaginal implants such as intravaginal rings (IVRs) and intrauterine devices rely on simple drug diffusion for drug delivery. The method of fabrication results in a matrix-based system that only allows diffusion of small molecule drugs from the polymer. Based on these current designs, it would not be possible to deliver nucleic acids, proteins/peptides, or nanocarrier systems from the implant systems. A major challenge in the materials science field is the development of precisely tuned stimuli-responsive drug delivery systems that can produce predictable drug release rates. As a result, the proposed research program is focused on the development of advanced biomaterials for the fabrication of bacteria-responsive IVRs that will provide controlled sustained delivery of antibiotic-encapsulated nanoparticles for >14 days. Initial focus will be on the fabrication of IVRs synthesized from novel polyurethane composite biomaterials that alter its composition in the presence of specific bacterial enzymes. These IVRs are designed to respond to changes to the microflora environment of the female genital tract e.g. little to no drug release at normal physiological conditions and rapid drug release when specific enzymes are released by foreign bacteria. Physical-chemical characterization of the newly synthesized biomaterials will be performed to determine properties such as melting temperature, porosity, shore hardness, etc. The influence of these various properties on the structural features of the fabricated IVRs and its impact on the release profile of antibiotic-encapsulated nanoparticles will also be investigated. The implant drug delivery system will be evaluated for biocompatibility, its ability to release drug in the presence of specific bacteria, long-term stability, and efficacy in reducing bacterial growth. Overall, the proposed research program is innovative and will significantly contribute to the advancement of knowledge in the field of materials science, via the generation of novel bacteria-responsive polyurethane composite biomaterials for the controlled delivery of nanoparticles. Most importantly, highly qualified personnel trained in this research program will acquire the necessary knowledge and skills to be leaders in the fields of biopolymers, materials engineering, and drug delivery.