Multipurpose tenofovir disoproxil fumarate electrospun fibers for the prevention of HIV-1 and HSV-2 infections in vitro

Int J Pharm. 2017 Oct 5;531(1):118-133. doi: 10.1016/j.ijpharm.2017.08.061. Epub 2017 Aug 7.

Abstract

Sexually transmitted infections affect hundreds of millions of people worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir disoproxil fumarate (TDF), exhibited sustained-release for up to 4 weeks, and provided complete in vitro protection against HSV-2 and HIV-1 for 24h and 1 wk, respectively, based on the doses tested. In vitro cell culture and EpiVaginal tissue tests confirmed the safety of fibers in vaginal and cervical cells, highlighting the potential of PLGA and PLCL EFs as multipurpose next-generation drug delivery vehicles.

Keywords: Antiretroviral (ARV); Drug delivery fiber; Electrospun fiber; HIV; HSV-2; MPT; Microbicide; Multipurpose prevention; Sexually transmitted infections (STIs); Sustained release fiber; Tenofovir (TFV); Tenofovir disoproxil fumarate (TDF).

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cervix Uteri / cytology
  • Drug Carriers / chemistry*
  • Female
  • HIV-1 / drug effects*
  • Herpesvirus 2, Human / drug effects*
  • Humans
  • Lactic Acid / chemistry
  • Polyesters / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tenofovir / pharmacology*
  • Vagina / cytology

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • Drug Carriers
  • Polyesters
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • lactide-caprolactone copolymer
  • Tenofovir