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

用于粘膜暴露前预防的抗 HIV 结直肠纳米载体泡沫

• 批准号: 8890332
• 负责人: Patrick J. Sinko
• 金额: $ 53.57万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8890332
• 关键词: AIDS prevention; Adverse effects; Affect; Anti-HIV Agents; Apoptotic; Area; Artificial nanoparticles; Bac7; Cells; Chronic; Colon; Colorectal; Counseling; Development; Distal; Dose; Drug Controls; Drug Exposure; Drug Formulations; Drug Kinetics; Engineering; FDA approved; Film; Frequencies; Goals; HIV; HIV Infections; Human immunodeficiency virus test; Infection; Injectable; Intestines; Intravenous; Lamina Propria; Medicine; Metabolism; Methods; Mucous Membrane; Mucous body substance; Mus; Nanotechnology; Oral; Patients; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Polymers; Prevention; Property; Prophylactic treatment; Randomized Clinical Trials; Rectum; Regimen; Research; Residual volume; Risk; Safe Sex; Series; Sleep; Surface; System; Technology; Tenofovir; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Ursidae Family; Vagina; Viral; base; compliance behavior; condoms; dosage; emtricitabine; experience; innovation; meetings; men; men who have sex with men; microbicide; nanocarrier; nanoparticle; novel; novel strategies; prevent; programs; public health relevance; rectal; success; truvada; uptake

 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.

 描述（由申请人提供）：在美国，与男性同睡的男性比任何其他群体更容易受到艾滋病毒感染的影响，占每年新感染的绝大多数。暴露前预防 (PrEP) 是 FDA 批准的唯一 HIV 预防方法，只有患者按处方服药才能有效减少感染。很遗憾， 最近口服 PrEP 的经验表明，大多数患者没有定期服药。在该研究项目中，将开发一种基于纳米技术的药物泡沫，每周直肠给药一次，以防止形成永久性艾滋病毒感染。抗艾滋病毒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。将同时研究两组治疗药物，即抑制性抗逆转录病毒药物和 TRAP（细胞凋亡能力的治疗恢复）药物。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。该项目接下来将开发纳米颗粒，这些纳米颗粒会被直肠和结肠组织吸收并在局部保留一周。对于每种药物，多组纳米颗粒将被设计为具有不同的延迟和释放时间，以便在组织中实现长达一周的有效药物暴露。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，可以大大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。