IGF::OT::IGF - IND ENABLING DEVELOPMENT OF NANOGMP: TARGETED

IGF::OT::IGF - IND 促进 NANOGMP 的开发：有针对性

• 批准号: 8857610
• 负责人: JUN LI
• 金额: $ 88.84万
• 依托单位: QUALIBER, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-20 至 2015-05-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8857610
• 关键词: Animals; Biodistribution; Clinical; Contracts; Development; Dose; Drug Kinetics; Effectiveness; Funding; Half-Life; Investigational Drugs; Laboratories; Lipids; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Modeling; Nanotechnology; Non-Small-Cell Lung Carcinoma; Pancreas; Patients; Phase; Predisposition; Resistance development; Rodent; Safety; Schedule; Small Business Innovation Research Grant; Therapeutic; Toxic effect; Toxicology; Tumor-Derived; Xenograft procedure; calcium phosphate; cancer cell; chemotherapy; gemcitabine; improved; malignant breast neoplasm; mouse model; nanoparticle; novel; scale up

Gemcitabine is a chemotherapy approved for several cancers, including non-small cell lung cancer, pancreatic, breast and ovarian cancer. However, its use has been limited due to its short half-life, susceptibility to resistance development and significant systemic toxicity. This SBIR Phase II contract proposal progresses NanoGMP, a product previously funded by Phase I SBIR contract, toward exploratory Investigational New Drug (IND) studies. NanoGMP utilizes novel targeted Lipid-Calcium-Phosphate (LCP) nanoparticle platform for the delivery of gemcitabine monophosphate (GMP) to cancer cells. NanoGMP has significantly improved efficacy and tolerability compared to gemcitabine in lung and pancreatic cancer mouse models. Under this proposal, NanoGMP will be manufactured in larger batches and utilized for non-clinical IND enabling studies. The studies will include exploratory non-GLP toxicology studies in three animal species, PK/biodistribution, and determination of optimal dose and schedule in standard xenograft and patient-derived tumor models. Furthermore, NanoGMP batches will be extensively characterized at NCI's Nanotechnology Characterization Laboratory. Results from these non-clinical studies will augment other IND enabling studies for completion of IND filing. Development of NanoGMP will improve the effectiveness and safety of a known chemotherapy, creating a "targeted chemotherapy" that enhances the potential for clinical benefit to patients with pancreatic, lung and other cancers.

吉西他滨是一种被批准用于治疗多种癌症的化疗药物，包括非小细胞肺癌、胰腺癌、乳腺癌和卵巢癌。然而，由于其半衰期短、易产生耐药性和显着的全身毒性，其使用受到限制。该 SBIR 第二阶段合同提案将 NanoGMP（之前由第一阶段 SBIR 合同资助的产品）推进到探索性研究性新药 (IND) 研究。 NanoGMP 利用新型靶向脂质钙磷酸盐 (LCP) 纳米颗粒平台将单磷酸吉西他滨 (GMP) 递送至癌细胞。与吉西他滨相比，NanoGMP 在肺癌和胰腺癌小鼠模型中显着提高了疗效和耐受性。根据该提案，NanoGMP 将进行大批量生产，并用于非临床 IND 研究。这些研究将包括对三种动物物种的探索性非 GLP 毒理学研究、药代动力学/生物分布，以及在标准异种移植和患者来源的肿瘤模型中确定最佳剂量和时间表。此外，NanoGMP 批次将在 NCI 的纳米技术表征实验室进行广泛的表征。这些非临床研究的结果将补充其他 IND 使研究能够完成 IND 申请。 NanoGMP的开发将提高已知化疗的有效性和安全性，创造一种“靶向化疗”，增强胰腺癌、肺癌和其他癌症患者的临床获益潜力。