Engineering intravaginal rings for HIV prevention and contraception

Update item information
Publication Type dissertation
School or College College of Engineering
Department Bioengineering
Author Clark, Justin Thomas
Title Engineering intravaginal rings for HIV prevention and contraception
Date 2014-05
Description Three decades have passed since the discovery of HIV and still no viable vaccine technologies exist to prevent the spread of the virus. The concept of interrupting HIV transmission with oral or topical antiretroviral drugs (ARV), also known as pre-exposureprophylaxis (PrEP), has been proven in several clinical efficacy trials. One PrEP strategy has been to formulate the ARV tenofovir (TFV) into topically applied vaginal gels. However, the vaginal gel approach has met with mixed results, likely due to poor user adherence. Globally, high incidence of HIV infection correlates with high incidence of unintended pregnancy, especially in resource-poor regions. Combining HIV PrEP with contraception into a single, easy-to-use product could have a synergistic effect, further motivating women to protect themselves against HIV infection. Thus, a concerted effort is underway to develop long-acting multipurpose prevention technologies (MPT) capable of simultaneously preventing sexual HIV transmission and pregnancy. The nearly half-century-old technology of the intravaginal ring (IVR) has undergone a renaissance in the past decade due to the potential of IVR to leverage both the principles of topical HIV PrEP and of long-acting controlled drug release systems. This dissertation details several new observations and innovations regarding drug delivery from intravaginal rings (IVR). First, an injection-molded, hydrophilic poly(ether urethane) (HPEU) matrix IVR capable of sustained release of milligram-per-day quantities of TFV over 90 days is described. In the final two chapters, a secondiv generation reservoir TFV IVR is combined with a reservoir poly(ether urethane) segment that releases microdoses of the contraceptive progestin levonorgestrel (LNG), in a multisegment IVR design, concluding with assessments of product stability and in vivo pharmacokinetics in order to confirm the suitability of the IVR for clinical investigation. This dissertation represents an engineer's approach to designing and testing IVR, which are most commonly considered a pharmaceutical product rather than a medical device. Accordingly, much attention is given to the development and usage of mathematical models for drug release and mechanical properties from IVR, and in general to a mechanistic understanding of the underlying mechanisms of their operation.
Type Text
Publisher University of Utah
Subject Contraception; HIV prevention; Intravaginal rings; Mathematical modeling; Pharmacokinetics; Vaginal drug delivery
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Rights Management Copyright © Justin Thomas Clark 2014
Format Medium application/pdf
Format Extent 2,643,164 Bytes
Identifier etd3/id/2839
ARK ark:/87278/s674003d
Setname ir_etd
Date Created 2014-05-08
Date Modified 2017-06-15
ID 196412
Reference URL