title: Reformulated tenofovir gel for use as a dual compartment microbicide.
abstract: OBJECTIVE
  Coital use of 1% tenofovir gel was shown to be modestly effective at preventing HIV transmission when applied vaginally in the CAPRISA 004 trial. Because the gel is hyperosmolar, which would reduce the integrity of the epithelium and induce fluid movement into the lumen, rectal use may not be acceptable. This study evaluated the pre-clinical safety and efficacy of a reformulated (reduced osmolality) tenofovir gel product.
  
  
  METHODS
  Reduced glycerine (RG)-tenofovir gel was compared with the original tenofovir gel for physiochemical characteristics, product safety and anti-HIV-1 activity.
  
  
  RESULTS
  The formulations were similar in all characteristics except for osmolality and spreadability/firmness. The RG-tenofovir gel had a 73% lower osmolality, a 29.6% increase in spreadability and a 27% decrease in firmness as compared with the original tenofovir gel. When applied to epithelial cell monolayers, tenofovir gel showed a transient reduction in the transepithelial resistance while the RG-tenofovir gel did not. Both gels retained ectocervical and colorectal explant viability. However, tenofovir gel treatment resulted in epithelial stripping that was absent after RG-tenofovir gel treatment of the polarized explants. Anti-HIV-1 activity was confirmed by lack of HIV-1 infection in polarized explants treated with either gel as compared with the control explants.
  
  
  CONCLUSIONS
  Reducing the osmolality of the tenofovir gel resulted in improved epithelial integrity, which suggests better safety upon rectal use. The improved gel safety did not compromise drug release or anti-HIV-1 activity. These data support the use of this gel as a dual compartment microbicide.
authors.affiliation: University of Pittsburgh, Pittsburgh, PA 15213, USA. cdezzutti@mwri.magee.edu
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Rohan
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: Uranker
authors.forename: Cory
authors.initials: C
authors.lastname: Shetler
authors.forename: Marilyn
authors.initials: M
authors.lastname: Cost
authors.forename: J D
authors.initials: JD
authors.lastname: Lynam
authors.forename: David
authors.initials: D
authors.lastname: Friend
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009924:Organ Culture Techniques; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D012007:Rectum / Q000187:drug effects / Q000502:physiology; D000068698:Tenofovir; D016896:Treatment Outcome; D014621:Vagina / Q000187:drug effects / Q000502:physiology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D063065:Organophosphonates; D014622:Vaginal Creams, Foams, and Jellies; D000068698:Tenofovir; D000225:Adenine