TRANSPORT AND ACTIVITY OF MICROBICIDES FORMULATIONS

该项目广泛的长期目标是更好地了解活性和赋形剂杀微生物剂在阴道/宫颈组织中的转运动力学，评估赋形剂对生殖道成分以及包括艾滋病毒在内的性病病原体的影响，并将这些因素的知识纳入辛基甘油的配方策略中。已经开发出的药物显示出作为杀微生物剂的抗性传播疾病的活性物质的前景。然而，有关活性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，这些制剂可能用于局部杀微生物剂配方。因此，本项目的具体目标是：1)利用Franz细胞扩散模型确定亲水性和亲脂性低分子化合物在阴道和宫颈组织中的传输动力学；2)评估配方辅料对活性杀菌剂通过阴道和宫颈组织的传输的影响；3)评估配方成分对淋球菌、沙眼衣原体、皱纹乳杆菌、阴道毛滴虫和其他生殖道能力的体外活性；4)与第二个项目中的Isaacs博士合作开发辛基甘油配方，5)使用传统的药物剂型评价技术评估开发的辛基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价单个制剂成分和配方产品对抗艾滋病毒和与第一个项目合作的猪尾猕猴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.