TRANSPORT AND ACTIVITY OF MICROBICIDES FORMULATIONS

该项目的长期目标是更好地了解活性和赋形剂杀微生物剂通过阴道/宫颈组织的运输动力学，评估赋形剂对生殖道成分以及包括HIV在内的性病病原体的影响，并将这些因素的知识纳入含有或不含肽的辛酰甘油的配方策略中。已经开发出的药物有望作为抗性传播疾病的活性剂，如杀菌剂。然而，关于可用于局部杀微生物剂配方的活性剂和赋形剂在阴道和宫颈组织中的转运动力学的基本信息很少。因此，该项目的具体目标是：1)利用Franz细胞扩散模型确定亲水性和亲脂性低分子量化合物通过阴道和宫颈组织的转运动力学；2)评估制剂辅料对活性杀微生物剂通过阴道和宫颈组织转运的影响；3)评估制剂成分对淋病奈瑟菌、沙眼衣原体、crispatus、阴道毛滴虫和生殖道的其他生物与科芯合作，与艾萨克斯博士合作，根据第二个项目的建议，开发一种辛酯甘油的配方；5)使用传统药物剂型评估技术评估所开发的辛酯甘油制剂的物理和化学性质；6)与第三个项目合作，在组织模型系统中评估单个配方成分和配方产品对艾滋病毒的有效性；与第一个项目合作，在长尾猕猴中评估对沙眼衣原体的有效性。

The broad long-term goals of this project are to better understand the kinetics of transport of active and excipient microbicide agents through vaginal/cervical tissue, to evaluate the effects of excipients on components of the genital tract as well as STD pathogens including HIV, and to incorporate knowledge of these factors into formulation strategies for octyl glycerol with or without peptides. Remedies have been developed which show promise as active agents against STDs as microbicides. However, very little basic information has been generated regarding the transport kinetics in vaginal and cervical tissues for active and excipient agents which may be used in topical microbicide formulations. Therefore, the specific aims of this project are to: 1) define the transport kinetics of hydrophilic and lipophilic low molecular weight compounds through vaginal and cervical tissue using a Franz cell diffusion model, 2) assess the impact of formulation excipients on transport of active microbicide agents through vaginal and cervical tissue, 3) evaluate the in vitro activity of formulation components on Neisseria gonorrhoeae, Chlamydia trachomatis, Lactobacillus crispatus, Trichomonas vaginalis and other competents of the genital tract in collaboration with the Cores 4) develop a formulation for octyl glycerol in collaboration with Dr. Isaacs as proposed in the second Project, 5) assess the physical and chemical properties of the developed octyl glycerol formulation using traditional pharmaceutical dosage form evaluation techniques and 6) evaluate the effectiveness of individual formulation components and formulated products against HIV in a tissue model system in collaboration with the third project and against Chlamydia trachomatis in the pig-tailed macaque in collaboration with the first Project.