Objectives: To assess the safety and distribution of a cellulose acetate 1,2-benzenedicarboxylate (CAP) gel formulation in rhesus macaques as part of the development process for its use as a vaginally administered product in humans.
Design: The similarities between the reproductive physiology, anatomy and vaginal microflora of human and non-human primates makes non-human primates a relevant animal model to assess the safety and distribution of candidate anti-HIV microbicides.
Methods: CAP gel was instilled once or once daily for 4 days into the vaginal vault of rhesus macaques. Colposcopy and magnetic resonance imaging were performed to detect adverse effects and spread of CAP, respectively. Additionally, vaginal pH and composition of the vaginal micorflora in macaques before, during and after CAP instillations were determined, and vaginal biopsies obtained following repeated CAP exposures were examined to further document its safety.
Results: CAP is safe for repeated use and exhibits a favorable distribution profile, showing no evidence of penetration into cells that line the vaginal epithelium. Further, the presence of CAP has no adverse effect on vaginal pH or the composition of the vaginal microflora, and does not induce vaginal epithelial thinning or inflammation.
Conclusions: CAP gel shows minimal toxicity in vivo, supporting its use as a candidate vaginal microbicide in humans.