Preclinical safety and efficacy assessments of dendrimer-based (SPL7013) microbicide gel formulations in a nonhuman primate model.

Abstract

Three gel formulations (1%, 3%, and 5% [wt/wt]) of SPL7013, a dendrimer known to have antiviral (anti-human immunodeficiency virus and anti-herpes simplex virus) activities, completed a range of preclinical tests in the pigtailed macaque models for vaginally and rectally applied topical microbicide safety assessments. The vaginal safety profile of the 3% SPL7013 gel formulation was equal to that of the 1% formulation but was superior to that of the 5% formulation. The 3% SPL7013 gel was further evaluated for rectal safety and for antichlamydial efficacy with cervical challenge with Chlamydia trachomatis. This first-generation dendrimer-based product was shown to be safe to the vaginal and rectal microenvironments with repeated daily use. However, a single intravaginal application of the 3% (wt/wt) SPL7013 gel did not provide protection from the acquisition of cervical chlamydial infection.

• Authors: D L Patton, Y T Cosgrove Sweeney, T D McCarthy, S L Hillier
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 50 Issue 5 Pg. 1696-700 (May 2006) ISSN: 0066-4804 [Print] United States
• PMID: 16641437 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Infective Agents
• Dendrimers
• Gels
• Polylysine
• astodrimer

Topics

• Animals
• Anti-Infective Agents (administration & dosage, adverse effects, pharmacology)
• Chlamydia Infections (prevention & control)
• Chlamydia trachomatis (drug effects)
• Dendrimers (chemistry)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Female
• Gels
• Macaca nemestrina
• Polylysine (administration & dosage, adverse effects, pharmacology)
• Rectum (microbiology, pathology)
• Vagina (microbiology, pathology)