OTHER FUNCTIONS - R&D BIOMEDICAL (BASIC RESEARCH)

其他功能-R

基本信息

批准号：
8564720
负责人：
CHARLES NOBLE
金额：
$ 21.6万
依托单位：
ZONEONE PHARMA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-15 至 2013-06-19
项目状态：
已结题

项目摘要

The Hsp90 inhibitor 17-DMAG will be encapsulated in a nano-sized liposome formulation that is long-circulating with controlled drug release properties in tumor tissue. Reformulation of 17-DMAG in a nanoliposome will increase the dose intensity of 17-DMAG in solid tumors while reducing the hepatic, gastrointestinal, nausea and bone marrow toxicity. The key is devising a nanoliposome composition that will retain the drug in circulation and release the drug from the nanoliposome at an appropriate rate after accumulation in the tumor. ZoneOne Pharma will use a new class of sterol-modified lipids (SML) that enable a wide and predictable range of drug release rates from the nanoliposome to encapsulate 17-DMAG using a remote loading protocol. In this development plan, ZoneOne Pharma will design nanoliposome compositions of 17-DMAG for evaluation by loading efficiency, in vitro plasma stability, in vivo pharmacokinetic and biodistribution studies. These formulations will be evaluated for tumor release effect on therapeutic activity in a proof-of-concept efficacy study at the end of Phase 1. A single formulation will be selected from confirmation efficacy studies as the first step of a future Phase II project.

HSP90抑制剂17-DMAG将封装在纳米大小的脂质体配方中，该制剂长期循环，在肿瘤组织中具有受控的药物释放性能。纳米脂体中17-DMAG的重新制定将增加实体瘤中17-DMAG的剂量强度，同时减少肝，胃肠道，恶心和骨髓毒性。关键是设计一种纳米脂质体组成，该组合物将在肿瘤中积累后以适当的速度将药物保留在循环中，并从纳米骨体中释放该药物。 ZoneOne Pharma将使用新的固醇改性脂质（SML），该脂质（SML）可以通过远程加载方案封装从纳米型体的广泛且可预测的药物释放率范围来封装17-DMAG。在此开发计划中，ZoneOne Pharma将通过负载效率，体外血浆稳定性，体内药代动力学和生物分布研究设计17-DMAG的纳米型体组成，以评估。这些制剂将在第1阶段结束时在概念验证疗效研究中评估肿瘤释放对治疗活性的影响。将从确认功效研究中选择单个配方作为未来II期项目的第一步。