Woodrow, Kim ABlakney, Anna2017-02-142017-02-142016-10Blakney_washington_0250E_16551.pdfhttp://hdl.handle.net/1773/38063Thesis (Ph.D.)--University of Washington, 2016-10Women are disproportionately affected by the HIV epidemic, especially in sub-Saharan Africa, where the majority of the world’s HIV burden is located. The development of female-initiated protection methods is motivated by the gender power disparity between men and women, which often leads to inability for women to negotiate condom use and/or faithfulness, coupled with the greater risk of male-to-female than female-to-male transmission per sex act. The current prevention strategy, referred to as ‘microbicides’, is to incorporate one or more antiretroviral drugs into a delivery vehicle, such gels, intravaginal rings, tablets, films, and injectables, all of which are in varying stages of development. Recently, electrospun fibers have been explored in proof-of-concept studies as a novel microbicide delivery vehicle. Drug-eluting fibers offer a number of advantages including the possibility of discreet use by women, the potential for easy scale-up, the ability to incorporate multiple physicochemically diverse drugs, and the use of different polymers and microarchitecture to tailor release of active compounds. Here, we investigate the role of formulation, including microarchitecture and the use of novel polyurethane polymers, on in vitro release of antiretroviral drug combinations with varying physicochemical properties. We have developed a pre-clinical in vitro hydrogel release model that allows for rapid, high throughput and anisotropic evaluation of microbicide formulations. Finally, we tested two formulations of electrospun fibers containing a triple-antiretroviral combination for safety and efficacy against RT-SHIV challenge in a nonhuman primate model.application/pdfen-USAntiretroviralCo-deliveryElectrospun fibersHIVMicrobicideBiomedical engineeringbioengineeringThesis