Forumlation Development and Selection of DuoGels and Smart Suppositories

项目总结（见说明）： 由于接受性肛交的实践并不限于与男性发生性关系的男性（MSM），并且有明确的证据表明在同一性行为中接受性阴道性交和肛交，因此开发适合直肠和阴道应用的杀微生物剂制剂是有充分理由的。双室杀微生物剂配方将降低为同时进行肛交和阴道性交的妇女维持单独剂型的复杂性。随着IQP-0528/TFV复方阴道凝胶的开发前景看好，将在项目1中利用现有凝胶制剂开发一种新型阴道和直肠双重凝胶（DuoGel）。此外，为了直接解决双室杀微生物剂产品中用户可接受性和阴道与直肠之间的生理差异的潜在问题，将开发一种“智能”栓剂装置，该装置将对环境变化做出响应，以理想地用于阴道或直肠递送。DuoGel开发将包括通过基于核心B（凝胶PK和凝胶铺展）定义的选择标准进行流变学、抗病毒、体外和离体毒性和安全性评价的IQP-0528单药制剂和IQP-0528/TFV复方制剂。 核心C（杀微生物剂功效和剂量）和项目2（来自MTSA的API浓度）。智能栓剂将通过pH敏感纳米颗粒对阴道和直肠中不断变化的pH差异做出反应，该pH敏感纳米颗粒将释放pH维持盐，以促进药物递送的理想环境。项目1、核心B和核心C之间的迭代评价将确定在动物试验中向前推进的凝胶和栓剂制剂（项目3）。

PROJECT SUMMARY (See instructions): As the practice of receptive anal intercourse is not limited to men who have sex with men (MSM), and there is clear evidence of both receptive vaginal and anal intercourse in the same sexual act, there is a strong rationale for the development of a microbicide formulation that is suitable for both rectal and vaginal application. A dual compartment microbicide formulation will reduce the complexity of maintaining separate dosage forms for women who engage in both anal and vaginal sex. With the promising development of the IQP-0528/TFV combination vaginal gel, a novel dual vaginal and rectal gel (DuoGel) will be developed in Project 1 from the preexisting gel formulation. In addition, to directly address potential issues of user acceptability and physiological differences between the vagina and rectum in a dual chamber microbicide product, a "smart" suppository device will be developed that will respond to environmental changes to beideal for either vaginal or rectal delivery. The DuoGel development will comprise the formulation of a singleIQP-0528 product and the combination IQP-0528/TFV product through rheological, anti-viral, in-vitro, and exvivo toxicity and safety evaluations based on selection criteria defined by Core B (gel PK and gel spreading). Core C (microbicide efficacy and dosing), and Project 2 (API concentration from MTSA). The smart suppository will be developed to respond to the changing pH differences in the vagina and rectum through pH sensitive nanoparticles that will release pH maintaining salts to prompt ideal environment for drug delivery. Iterative evaluations between Project 1, Core B and Core C will identify a gel and suppository formulation to be moved forward in animal trials (Project 3).