Development and pharmacokinetics of a combination vaginal ring for sustained release of dapivirine and the protein microbicide 5P12-RANTES

John W. McBride, R. Karl Malcolm, Nicola Dias, David Cameron, Robin E. Offord, Oliver Hartley, Victoria L. Kett, Brid Devlin, Peter Boyd

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
49 Downloads (Pure)

Abstract

The past fifteen years have witnessed a resurgence of interest in vaginal ring technologies for drug delivery applications, mostly driven by the impetus for development of vaginally-administered antiretroviral microbicides to help reduce the high acquisition rates for human immunodeficiency virus (HIV) among Sub-Saharan African women. Currently, the lead candidate microbicide is a 28-day silicone elastomer vaginal ring releasing dapivirine (Ring-004), an experimental non-nucleoside reverse transcriptase inhibitor. The ring was tested in two pivotal Phase III clinical studies in 2016 and is currently undergoing review by the European Medicines Agency. Recently, we described a new type of silicone elastomer vaginal ring offering sustained release of the protein molecule 5P12-RANTES, a potent experimental chemokine analogue that potently blocks the HIV CCR5 coreceptor. Building on our previous work, here we report the preclinical development of a new combination vaginal ring that offers sustained release of both 5P12-RANTES and dapivirine, in which the 5P12-RANTES is incorporated into an exposed core within the ring body and the dapivirine in the sheath. In this way, in vitro release of dapivirine matches closely that for Ring-004. Also, we report the pharmacokinetic testing of this combination ring formulation in sheep, where vaginal concentrations of both drugs are maintained over 28 days at levels potentially useful for preventing HIV infection in women.
Original languageEnglish
Pages (from-to)207-213
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume564
Early online date15 Apr 2019
DOIs
Publication statusPublished - 10 Jun 2019

Keywords

  • Antiretroviral
  • Combination drug delivery
  • HIV microbicide
  • HIV prevention
  • Sheep pharmacokinetics
  • Silicone elastomer

ASJC Scopus subject areas

  • Pharmaceutical Science

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