OTHER FUNCTIONS TAS:: 750849 REFORMULATION OF CANCER THERAPEUTICS USING NANOTECH

其他功能 TAS:: 750849 使用纳米技术重新制定癌症治疗方法

• 批准号: 8564721
• 负责人: WALTER MCCONATHY
• 金额: $ 19.13万
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2013-06-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8564721
• 关键词: Antineoplastic Agents; Biocompatible; Chemicals; Dose-Limiting; Drug Delivery Systems; Drug Formulations; Goals; High Density Lipoproteins; In Vitro; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Modeling; Mus; Nanotechnology; Pharmaceutical Preparations; Safety; Solubility; Therapeutic Uses; Toxic effect; Treatment Efficacy; Tumor Suppression; base; cancer cell; cytotoxicity; improved; nanoparticle; novel; ovarian neoplasm; receptor; reconstitution; water solubility

The aim of this project is to reformulate a highly lipophilic anti-cancer agent, valrubicin (AD-32) that has only been approved for vesicular treatment of bladder cancer due to its poor dose limiting toxicities due to poor water solubility. LipoMedics will reformulate valrubicin (AD-32) utilizing a robust, novel biocompatible drug delivery system, composed of reconstituted high density lipoprotein (rHDL) nanoparticles that are particularly effective in improving solubility and safety of poorly soluble drugs. The additional advantage of formulating drugs with rHDL is the selective targeting toward malignant tumors via the SR-B1 receptor. LipoMedics intends to conduct proof of concept studies to evaluate therapeutic efficacy of the rHDL/AD-32 drug formulation versus that of the free drug. These studies will include assessment of cytotoxicity versus cancer cells, stability of the rHDL/AD-32 formulation and tumor suppression studies in mice. The major goal of these studies is to demonstrate enhancement in therapeutic efficacy of AD-32 via encapsulation in rHDL nanoparticles. Based on previous studies, it is anticipated that AD-32, as an initial model, and subsequently a wide range of similarly lipophilic drugs, can be reformulated to produce clinically effective anti-cancer drugs as well as profitable ventures for biotech entrepreneurs.

该项目的目的是重新配制一种高度亲脂性的抗癌剂，戊柔比星（AD-32），由于其水溶性差而导致的剂量限制性毒性差，仅被批准用于膀胱癌的囊泡治疗。LipoMedics将重新制定戊柔比星（AD-32）利用一个强大的，新的生物相容性药物输送系统，组成的重组高密度脂蛋白（rHDL）纳米粒子，特别是有效地提高溶解度和安全性的难溶性药物。用rHDL配制药物的另一个优点是通过SR-B1受体选择性靶向恶性肿瘤。LipoMedics计划进行概念验证研究，以评价rHDL/AD-32药物制剂与游离药物的治疗效果。这些研究将包括评估对癌细胞的细胞毒性、rHDL/AD-32制剂的稳定性和小鼠肿瘤抑制研究。这些研究的主要目标是证明通过包封在rHDL纳米颗粒中AD-32的治疗功效的增强。根据以前的研究，预计AD-32作为初始模型，以及随后的各种类似的亲脂性药物，可以重新配制，以生产临床有效的抗癌药物以及生物技术企业家的盈利企业。