A targeted anti-HIV drug delivery to the GALT

向 GALT 输送靶向抗 HIV 药物

• 批准号: 10431955
• 负责人: Upal Roy
• 金额: $ 31.47万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-16 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10431955
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Anti-HIV Agents; Anti-HIV Therapy; Anti-Retroviral Agents; Antibodies; Antigens; 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; Persons; Peyer' 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

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）仍然是全世界主要的死亡原因之一 主要是在资源有限的国家。目前的联合抗逆转录病毒疗法（cART） 大大降低了患者的疾病死亡率。然而，病毒仍然存在， 病毒储库器官，如肠相关淋巴组织（GALT）。大多数cART药物 由于其复杂的生理机制，未能根除GALT储库。在这方面， 特别是在治疗水平下延伸到远端淋巴组织 时间将是当前的兴趣。考虑到下一代HIV-1疗法是 艾滋病研究办公室的优先研究领域，我们建议开发一种基于纳米医学的 靶向GALT中的微折叠细胞（M细胞）的长效抗HIV药物制剂。M细胞是 主要存在于胃肠道中的特化上皮细胞。它有效 将许多小分子转运到粘膜免疫系统。考虑 由于M-细胞的转胞吞性质，我们开发了一种含有三个 目前推荐的抗艾滋病毒药物（也称为纳米药物）。这种纳米药物是生物结合的 与抗M细胞特异性抗体一起用于靶向药物递送至M细胞。我们假设M- 细胞介导的药物递送将比常规药物更持久和有效地递送到 GALT。