Engineering a degradable polyurethane intravaginal ring for sustained delivery of dapivirine

Drug Delivery and Translational Research
Manpreet KaurPatrick F Kiser

Abstract

We describe the engineering of a degradable intravaginal ring (IVR) for the delivery of the potent HIV-1 reverse transcriptase inhibitor dapivirine. The degradable polymer used in fabricating the device incorporated poly(caprolactone) ester blocks in a poly(tetramethylene ether) glycol ABA type polyurethane backbone. The polymer was designed to maintain its structure for 1 month during usage and then degrade in the environment post-disposal. In vitro release of dapivirine showed zero-order kinetics for up to 1 month and significant levels of drug release into engineered vaginal tissue. The mechanical properties of the degradable IVR were comparable to those of a widely used contraceptive intravaginal ring upon exposure to simulated vaginal conditions. Incubation under simulated vaginal conditions for a month caused minimal degradation with minimal effect on the mechanical properties of the ring and polymer. The cytotoxicity evaluation of the drug-loaded IVRs against Vk2/E6E7 human vaginal epithelial cells, Lactobacillus jensenii, and engineered vaginal tissue constructs showed the degradable polyurethane to be non-toxic. In vitro evaluation of inflammatory potential monitored through the levels of inflammatory cytokines IL-8, I...Continue Reading

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Citations

Dec 26, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Susan M FetherstonR Karl Malcolm
Oct 25, 2016·Journal of Pharmaceutical Sciences·Ameya R KirtaneGiovanni Traverso
Sep 30, 2015·Antimicrobial Agents and Chemotherapy·Yannick Leandre TraoreEmmanuel A Ho
Apr 3, 2012·The Journal of Antimicrobial Chemotherapy·Pedro M M MesquitaBetsy C Herold
Jul 21, 2020·Expert Opinion on Drug Delivery·Peter BoydR Karl Malcolm
Jun 18, 2017·Pharmacological Reports : PR·Aleksandra AmelianKatarzyna Winnicka
May 12, 2018·Pharmaceutics·Michael B LowingerRobert O Williams
Jun 3, 2021·Pharmaceutics·Louise CarsonRobert Karl Malcolm
Apr 11, 2016·ACS Biomaterials Science & Engineering·Adrian J T TeoYong-Jin Yoon

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