Abstract Details

Presented By: Poursaid, Azadeh
Affiliated with: University of Utah, Biomedical Engineering
Authors: Kavita Gupta, Azadeh Poursaid, Manpreet Kaur, Patrick Kiser
From: Separ1Department of Biomedical Engineering, University of Utah, Salt Lake City, UT-84112
Title
DEVELOPMENT OF VAGINAL RING FOR DELIVERY OF TENOFOVIR
Abstract

INTRODUCTION

Tenofovir is an FDA approved nucleotide reverse transcriptase inhibitor of HIV, which is activated after intracellular metabolism and in turn terminates the proviral DNA systhesis of HIV. Tenofovir is safely tolerated during long term (up to 5 years) oral delivery as tenofovir disoproxil fumarate in HIV/AIDS patients. This proven safety along with a high intracellular retention time, > 72 hrs, has motivated the investigation of tenofovir in semi-solid gel dosage forms for prophylaxis of male-to-female transmission of HIV. We aim to further enhance the success of tenofovir as a microbicide by utilizing intravaginal rings (IVR) as the delivery strategy and thereby harness the high patient compliance associated with IVRs. We investigated the feasibility of delivering tenofovir and a hydrophilic model drug compound using IVRs fabricated from a medical grade polyether urethane (PU).

MATERIALS / METHODS

Thermal stability of Tenofovir was evaluated by NMR, LC/MS and DSC. A fabrication protocol was developed utilizing melt-extrusion at temperatures that does not compromise the stability of tenofovir. Release of tenofovir was evaluated under simulated physiological conditions and quantified by HPLC. Additionally, release of adenosine 5’ monophosphate (AMP), a model compound for tenofovir, was evaluated from PU matrix with PEG (Mn=2000) as an additive. The rationale for incorporation of PEG was to provide aqueous transport channels to facilitate the release of the hydrophilic model compound from hydrophobic PU matrix.

RESULTS

Thermal stability of tenofovir was confirmed upto temperatures of 150 °C. LC/MS analysis of tenofovir extracted from PU matrix prior to and after extrusion demonstrated no significant change in the spectrum. Release of tenofovir was shown from extruded PU matrix samples under simulated physiological conditions. Additionally, zero-order release of AMP was engineered by modifying the PU matrix with incorporation of PEG molecules.

CONCLUSION

Tenofovir released via polyurethane IVRs can be an effective strategy for long-duration prevention of sexual transmission of HIV.