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Combinatorial nanotechnology-based regimens for pancreatic cancer chemoprevention

基于组合纳米技术的胰腺癌化学预防方案

基本信息

批准号：
8771013
负责人：
SUNIL PRABHU
金额：
$ 43.8万
依托单位：
WESTERN UNIVERSITY OF HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-02 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8771013
关键词：
Animals Apoptosis Applications Grants Aspirin Biodistribution Biological Availability Blood Circulation Cell Survival Cells Centers for Disease Control and Prevention (U.S.)Chemoprevention Chemopreventive Agent Chitosan Curcumin Data Development Diagnosis Disease Progression Dosage Forms Dose Drug Combinations Drug Compounding Drug Delivery Systems Drug Formulations Drug Kinetics Effectiveness Encapsulated Ensure Future Generations Goals Hamsters Hepatic Immune In Vitro Incidence Intraepithelial Neoplasia Investigation Journals Kidney Lead Lipids Lymphatic Malignant Neoplasms Malignant neoplasm of pancreas Metabolism Modality Modeling Nanotechnology Oral Oral Administration Organ Outcome Pancreas Pathway interactions Patients Pharmaceutical Preparations Pilot Projects Prevention Research Publications Published Comment Publishing Regimen Reporting Research Route Site Solid Sulforaphane System Technology Therapeutic Time Tissues Toxic effect Transgenic Mice United States National Institutes of Health Universities Work base cancer chemoprevention cancer prevention clinical application combinatorial design improved in vivo mortality mouse model nano nanoparticle novel novel strategies outcome forecast pancreatic cancer cells public health relevance residence response tool trend tumor

项目摘要

DESCRIPTION (provided by applicant): The past two decades of research have proved unsuccessful in finding a viable treatment option for pancreatic cancer. As many cancer rates continue to decline, pancreatic cancer incidence and mortality is expected to increase going forward. Due to lack of suitable treatment modalities and <5% chances of survival upon diagnosis, an alternative approach lies in chemoprevention, using suitable agents that can inhibit or reverse the progression of this disease. Our group was the first to report a novel combinatorial approach of low concentrations of aspirin, curcumin and sulforaphane (ACS) administered via a nanotechnology-based oral drug delivery system using solid-lipid nanoparticles (SLNs). Results from these pilot studies, both in vitro and in vivo, showed significant synergistic decrease in cell viability, increased cell apoptosis and significant reducton in pancreatic intraepithelial neoplasms (PanINs) when using this novel approach. While these data appear to be promising for pancreatic cancer chemoprevention, many new questions remain unanswered. In this proposal, we are focused on further investigation of an ideal formulation strategy for long-term oral administration of ACS, using a second generation of SLNs conjugated with chitosan (c-SLN) for improved targeting of the pancreatic tissues. Additionally, we will look at toxicity profiles, pharmacokinetics and biodistribution in pancreatic tissue and ensure efficacy in a transgenic mouse model. Overall, based on our strong preliminary results and related publications, we believe the outcomes of this proposal will establish the groundwork to consider the ACS nano-regimen with c-SLNs as a viable approach for the chemoprevention of pancreatic cancer.

描述（由申请人提供）：过去二十年的研究已证明未能成功找到胰腺癌的可行治疗方案。随着许多癌症发病率持续下降，胰腺癌的发病率和死亡率预计未来将会增加。由于缺乏合适的治疗方式且诊断后生存率<5%，另一种方法是化学预防，即使用可以抑制或逆转这种疾病进展的合适药物。我们的研究小组首次报道了一种新的组合方法，通过使用固体脂质纳米粒子（SLN）的基于纳米技术的口服药物递送系统施用低浓度阿司匹林、姜黄素和萝卜硫素（ACS）。这些体外和体内初步研究的结果表明，使用这种新方法时，细胞活力显着协同降低，细胞凋亡增加，胰腺上皮内肿瘤 (PanIN) 显着减少。虽然这些数据似乎对胰腺癌化学预防很有希望，但许多新问题仍未得到解答。在本提案中，我们的重点是进一步研究长期口服 ACS 的理想配方策略，使用与壳聚糖 (c-SLN) 缀合的第二代 SLN 来改善胰腺组织的靶向性。此外，我们还将研究胰腺中的毒性特征、药代动力学和生物分布组织并确保在转基因小鼠模型中的功效。总体而言，基于我们强有力的初步结果和相关出版物，我们相信该提案的结果将为将带有 c-SLN 的 ACS 纳米方案视为胰腺癌化学预防的可行方法奠定基础。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel nano-drug combination therapeutic regimen demonstrates significant efficacy in the transgenic mouse model of pancreatic ductal adenocarcinoma.

新型纳米药物组合治疗方案在胰腺导管腺癌转基因小鼠模型中显示出显着疗效。

DOI：
发表时间：
2018
期刊：
American journal of cancer research
影响因子：
5.3
作者：
Thakkar,Arvind;Desai,Preshita;Chenreddy,Sushma;Modi,Jalpa;Thio,Astrid;Khamas,Wael;Ann,David;Wang,Jeffrey;Prabhu,Sunil
通讯作者：
Prabhu,Sunil

Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells.