Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy

PLoS One. 2014 Mar 5;9(3):e88509. doi: 10.1371/journal.pone.0088509. eCollection 2014.


The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-acting drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 µm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt% levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 µg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrated rings endured between 152 N and 354 N tensile load before failure during uniaxial extension testing. In summary, this system represents a significant advance in vaginal drug delivery technology, and is the first in a new class of long-acting multipurpose prevention drug delivery systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / pharmacokinetics
  • Contraceptive Devices, Female*
  • Drug Delivery Systems
  • Elasticity
  • Female
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • Humans
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / pharmacokinetics
  • Models, Theoretical
  • Polyurethanes / chemistry*
  • Pregnancy
  • Pregnancy, Unwanted*
  • Rabbits
  • Tensile Strength


  • Contraceptive Agents, Female
  • Polyurethanes
  • polyetherurethane
  • Levonorgestrel

Grants and funding

Funding was provided under cooperative agreement (GPO-A-00-08-00005-00 and AID-OAA-A-10-0006) between the United States Agency for International Development (USAID) and the Eastern Virginia Medical School. This work was supported by a cooperative agreement from The United States Agency for International Development (USAID). USAID had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.