Safety and distribution of cellulose acetate 1,2-benzenedicarboxylate (CAP), a candidate anti-HIV microbicide in rhesus macaques.
Safety and distribution of cellulose acetate 1,2-benzenedicarboxylate (CAP), a candidate anti-HIV microbicide in rhesus macaques.
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醋酸纤维素 1,2-苯二甲酸 (CAP) 的安全性和分布，它是一种候选抗 HIV 杀菌剂，在恒河猴中使用。
DOI：
10.1097/01.aids.0000185990.16477.47
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Blanchard,James
中科院分区：
文献类型：
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作者：
Ratterree,Marion;Gettie,Agegnehu;Williams,Victoria;Malenbaum,Susan;Neurath,ARobert;Cheng-Mayer,Cecilia;Blanchard,James
目的：评估醋酸纤维素1,2 -苯二甲酸酯（CAP）凝胶制剂在恒河猴体内的安全性和分布，作为其作为人类阴道给药产品的开发过程的一部分。设计：人类和非人灵长类动物在生殖生理、解剖和阴道菌群方面的相似性使非人灵长类动物成为评估候选抗hiv杀菌剂安全性和分布的相关动物模型。方法：在恒河猴阴道穹窿内滴注CAP凝胶1次或1次，连续4 d。阴道镜和磁共振成像分别检测CAP的不良反应和扩散情况。此外，在注射CAP之前、期间和之后，测定了猕猴阴道pH值和阴道菌群组成，并检查了反复接触CAP后获得的阴道活组织检查，以进一步证明其安全性。结果：CAP重复使用是安全的，并且表现出良好的分布特征，没有证据表明渗透到阴道上皮细胞中。此外，CAP的存在对阴道pH值或阴道菌群的组成没有不良影响，也不会引起阴道上皮变薄或炎症。结论：CAP凝胶在体内显示出最小的毒性，支持其作为人类阴道杀微生物剂的候选使用。
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.