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

本项目的目的是重新配制一种高度亲脂性的抗癌药物，valrubicin (AD-32)，由于其水溶性差，其剂量限制毒性较差，仅被批准用于膀胱癌的囊泡治疗。LipoMedics将利用一种强大的新型生物相容性给药系统重新配制valrubicin (AD-32)，该系统由重组的高密度脂蛋白（rHDL）纳米颗粒组成，在改善难溶性药物的溶解度和安全性方面特别有效。用rHDL配制药物的另一个优势是通过SR-B1受体选择性靶向恶性肿瘤。LipoMedics打算进行概念验证研究，以评估rHDL/AD-32药物制剂与游离药物的治疗效果。这些研究将包括对癌细胞的细胞毒性评估，rHDL/AD-32制剂的稳定性以及小鼠肿瘤抑制研究。这些研究的主要目的是证明通过在rHDL纳米颗粒中封装AD-32的治疗效果的增强。根据先前的研究，预计AD-32作为初始模型，以及随后广泛的类似亲脂性药物，可以重新配制，以生产临床有效的抗癌药物，并为生物技术企业家提供有利可图的风险投资。

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.