Engineering a degradable polyurethane intravaginal ring for sustained delivery of dapivirine

Manpreet Kaur, Kavita M. Gupta, Azadeh E. Poursaid, Prasoona Karra, Alamelu Mahalingam, Hyder A. Aliyar, Patrick F. Kiser

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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, IL-1α, IL-6, IL-1β, and MIP-3α when engineered EpiVaginal™ tissue was incubated with the polyurethanes suggested that the degradable polyurethane was comparable to commercial medical grade polyurethane. These results are encouraging for further development of this degradable IVR for topical vaginal delivery of microbicides.

Original languageEnglish (US)
Pages (from-to)223-237
Number of pages15
JournalDrug Delivery and Translational Research
Volume1
Issue number3
DOIs
StatePublished - Jun 1 2011

Keywords

  • Anti-HIV
  • Biodegradation
  • Dapivirine
  • Drug delivery/release
  • Mechanical properties
  • Microbicide
  • Polyurethane
  • Women's health

ASJC Scopus subject areas

  • Pharmaceutical Science

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