ANTI-HIV COLORECTAL NANOCARRIER-BASED FOAMS FOR MUCOSAL PRE-EXPOSURE PROPHYLAXIS

 描述(由申请者提供)：与男性发生性关系的男性比美国其他任何群体受艾滋病毒感染的影响都更严重，占每年新增感染人数的绝大多数。暴露前预防(PrEP)是FDA批准的唯一一种艾滋病毒预防方法，只有当患者按处方服用药物时，才能有效地减少感染。不幸的是， 最近口服PrEP的经验表明，大多数患者没有定期服药。在这项研究计划中，将开发一种基于纳米技术的药物泡沫，每周直肠给药一次，以防止建立永久性的艾滋病毒感染。抗HIV药物将从被吸收的纳米颗粒中释放出来，并在结肠和直肠组织中停留一周，治疗局部早期病毒暴露。两组治疗药物，抑制性抗逆转录病毒药物和TRAP(凋亡熟练度治疗回收)药物将同时进行研究。这项拟议的研究将通过首先配制直肠给药泡沫来实现其目标，该泡沫将含有药物的纳米颗粒散布到整个直肠和结肠。该计划下一步将开发纳米颗粒，这些纳米颗粒被吸收并在直肠和结肠组织中局部停留一周。对于每种药物，将对多组纳米颗粒进行改造，使其具有不同的延迟和释放时间，以实现药物在组织中的有效暴露长达一周。最后，将对含有工程纳米颗粒的泡沫进行临床前评估。这种新的治疗方案被称为粘膜PrEP，可能会大幅减少药物剂量和给药频率，从而减少副作用并提高患者的依从性。

 DESCRIPTION (provided by applicant): Men who sleep with men are more severely affected by HIV infection than any other group in the US, representing the vast majority of new infections each year. Pre-exposure prophylaxis (PrEP), the only FDA-approved HIV prevention method, is effective in reducing infection only if patients take their medicines as prescribed. Unfortunately, recent experience with orally administered PrEP indicates the majority of patients do not take their medications regularly. In this research program, a nanotechnology-based pharmaceutical foam administered rectally once a week will be developed to prevent the establishment of permanent HIV infection. Anti-HIV drugs will be released from nanoparticles that are absorbed and stay in colonic and rectal tissue for a week treating early viral exposure locally. Two groups of therapeutic agents, suppressive antiretrovirals and TRAP (therapeutic reclamation of apoptotic proficiency) agents, will be investigated in parallel. The proposed research will accomplish its objectives by first formulating rectally administered foams that spread drug- containing nanoparticles throughout the rectum and colon. The program will next develop nanoparticles that are taken up and remain locally for a week in rectal and colonic tissues. For each drug, multiple groups of nanoparticles will be engineered to have different delays and release times in order to achieve effective drug exposure in the tissue for up to a week. Finally, foams containing the engineered nanoparticles will be evaluated preclinically. This new treatment option, known as mucosal PrEP, may drastically reduce drug dosages and frequency of administration resulting in fewer side effects and increased patient compliance.