Development and evaluation of a thermosensitive vaginal gel containing raltegravir+efavirenz loaded nanoparticles for HIV prophylaxis

Antiviral Res. 2012 Dec;96(3):430-6. doi: 10.1016/j.antiviral.2012.09.015. Epub 2012 Oct 3.


The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL+EFV-NPs) for pre-exposure prophylaxis of HIV. RAL+EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL+EFV-NP were 81.8±6.4 nm and -23.18±7.18 mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5% and 98.2% respectively. Thermosensitive vaginal gel containing RAL+EFV-NPs was successfully prepared using a combination of Pluronic F127 (20% w/v) and Pluronic F68 (1% w/v). Incorporation RAL+EFV-NPs in the gel did not result in nanoparticle aggregation and RAL+EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL+EFV-NPs were evaluated for inhibition of HIV-1(NL4-3) using TZM-bl indicator cells. The EC(90) of RAL+EFV-NPs was lower than raltegravir+efavirenz (RAL+EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL+EFV-NPs or blank gel were not cytotoxic for 14 days in vitro. The intracellular levels of efavirenz in RAL+EFV-NPs treated HeLa cells were above the EC(90) for 14 days whereas raltegravir intracellular concentrations were eliminated within 6 days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30 min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Benzoxazines / chemistry
  • Benzoxazines / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cyclopropanes
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Evaluation, Preclinical
  • Gels / chemistry
  • Gels / pharmacology*
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HeLa Cells
  • Humans
  • Lactic Acid / chemistry
  • Microbial Sensitivity Tests
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Phagocytosis
  • Poloxamer / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / pharmacology*
  • Raltegravir Potassium
  • Temperature
  • Time Factors


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Drug Carriers
  • Gels
  • Pyrrolidinones
  • Poloxamer
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Raltegravir Potassium
  • efavirenz