A targeted anti-HIV drug delivery to the GALT

向 GALT 输送靶向抗 HIV 药物

基本信息

批准号：
10218032
负责人：
Upal Roy
金额：
$ 65.79万
依托单位：
UNIVERSITY OF TEXAS RIO GRANDE VALLEY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-16 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10218032
关键词：
Acquired Immunodeficiency Syndrome Acute Anti-HIV Agents Anti-HIV Therapy Anti-Retroviral Agents Antibodies Antigens Antiviral Agents Area Bacteria Binding CD34 gene Cause of Death Cell model Cells Collaborations Complex Country Data Digestion Disease Dose Drug Delivery Systems Drug Formulations Drug Kinetics Drug Targeting Encapsulated Enteral Environment Epithelial Formulation Gastrointestinal tract structure Glycoproteins Goals Gut associated lymphoid tissue HIV HIV-1 Immune In Vitro Inbred BALB C Mice Infection Institution Intestines Legal patent Link Lymphoid Follicle Lymphoid Tissue M cell Mediating Metabolic Metabolism Modeling Mucosal Immune System Mus NIH Office of AIDS Research Nanotechnology North Carolina Oral Oral Administration Organ Patients Peyer&apos s Patches Phagocytes Pharmaceutical Preparations Pharmacists Pharmacology Study Phase Physiology Pluronics Polymers Property Publications Publishing Recording of previous events Research Research Priority Residual state Resources Safety Site Specialized Epithelial Cell Stomach Structure Surface Technology Therapeutic Time Tissues Toxic effect Treatment Efficacy Treatment outcome United States National Institutes of Health Universities Viral reservoir Virus Work antiretroviral therapy base capsule cellular targeting drug release profile improved in vivo innovation interest mortality nanocarrier nanodrug nanoformulation nanomedicine next generation novel pharmacokinetics and pharmacodynamics side effect targeted agent targeted delivery therapy outcome transcytosis

项目摘要

Human Immunodeficiency Virus 1 (HIV-1) remains one of the leading causes of death worldwide predominantly in resource-limited countries. The present Combined Antiretroviral Therapy (cART) has significantly reduced disease mortality among patients. However, the virus still persists in viral reservoir organs such as Gut-associated lymphoid tissue (GALT). Mostly cART drugs have failed to eradicate GALT reservoir because of its complex physiology. In this regard, drugs that specifically reach out to that remote lymphatic tissue at therapeutic level for an extended period of time will be of current interest. Considering the next-generation therapy for HIV-1 as one of the priority research areas of Office of AIDS Research, we propose to develop a nanomedicine based long-acting anti-HIV drug formulation targeting Microfold cells (M-cell) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the gastrointestinal tract. It effectively transports many micromolecules to the underlying mucosal immune system. Considering the transcytosis property of M-cell, we have developed a pluronic nanocarrier containing three currently recommended anti-HIV drugs (also called nanodrug). This nanodrug is bio-conjugated with anti-M-cell specific antibody for targeted drug delivery to M-cell. We hypothesize that an M- cell mediated drug delivery will be more sustained and effective than conventional drugs to the GALT.

人类免疫缺陷病毒1（HIV-1）仍然是全球死亡的主要原因之一主要在资源有限的国家中。目前的抗逆转录病毒疗法（CART）患者的疾病死亡率大大降低。但是，病毒仍然持续存在病毒储层器官，例如肠道相关的淋巴组织（GALT）。主要是购物药由于其复杂的生理学，无法根除Galt水库。在这方面，吸毒特定在治疗水平的远程淋巴组织长时间接触时间将引起当前的关注。将HIV-1的下一代疗法视为其中之一优先研究艾滋病研究领域，我们建议开发基于纳米医学的长效抗HIV药物制剂靶向小圆形细胞（M细胞）。 M细胞是主要存在于胃肠道中的专门上皮细胞。它有效将许多微分子运输到潜在的粘膜免疫系统。考虑到 M-Cell的转胞病特性，我们开发了一个含有三个的Pluronic纳米载体目前推荐的抗HIV药物（也称为纳米果）。该纳米果是生物结合的抗M细胞特异性抗体用于靶向药物向M细胞递送。我们假设M- 细胞介导的药物输送将比常规药物更持续和有效加尔特。