Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine

Drug Des Devel Ther. 2014 Oct 9;8:1801-15. doi: 10.2147/DDDT.S71352. eCollection 2014.

Abstract

Hydroxychloroquine (HCQ) has been shown to demonstrate anti-inflammatory properties and direct anti-HIV activity. In this study, we describe for the first time the fabrication and in vitro evaluation of two types of intravaginal ring (IVR) devices (a surfaced-modified matrix IVR and a reservoir segmental IVR) for achieving sustained delivery (>14 days) of HCQ as a strategy for preventing male-to-female transmission of HIV. Both IVRs were fabricated by hot-melt injection molding. Surface-modified matrix IVRs with polyvinylpyrrolidone or poly(vinyl alcohol) coatings exhibited significantly reduced burst release on the first day (6.45% and 15.72% reduction, respectively). Reservoir IVR segments designed to release lower amounts of HCQ displayed near-zero-order release kinetics with an average release rate of 28.38 μg/mL per day for IVRs loaded with aqueous HCQ and 32.23 μg/mL per day for IVRs loaded with HCQ mixed with a rate-controlling excipient. Stability studies demonstrated that HCQ was stable in coated or noncoated IVRs for 30 days. The IVR segments had no significant effect on cell viability, pro-inflammatory cytokine production, or colony formation of vaginal and ectocervical epithelial cells. Both IVR systems may be suitable for the prevention of HIV transmission and other sexually transmitted infections.

Keywords: HIV/AIDS; drug release; intravaginal delivery; matrix system; microbicide; polymeric drug carrier; reservoir system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Drug Stability
  • Humans
  • Hydroxychloroquine / administration & dosage*
  • Hydroxychloroquine / chemistry
  • Hydroxychloroquine / pharmacology
  • Kinetics
  • Polyurethanes / chemical synthesis
  • Polyurethanes / chemistry*
  • Structure-Activity Relationship

Substances

  • Polyurethanes
  • polyetherurethane
  • Hydroxychloroquine