title: 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.affiliation: Department of Obstetrics and Gynecology, Box 356460, University of Washington, Seattle, WA 98195-6460, USA. dpatton@u.washington.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Patton
authors.forename: Y T
authors.initials: YT
authors.lastname: Cosgrove Sweeney
authors.forename: T D
authors.initials: TD
authors.lastname: McCarthy
authors.forename: S L
authors.initials: SL
authors.lastname: Hillier
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002690:Chlamydia Infections / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005782:Gels; D008254:Macaca nemestrina; D011107:Polylysine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D012007:Rectum / Q000382:microbiology / Q000473:pathology; D014621:Vagina / Q000382:microbiology / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents; D050091:Dendrimers; D005782:Gels; D011107:Polylysine; C480351:astodrimer