Collaborative Research: Polysaccharide Derivatives for Enhanced Drug Delivery

合作研究：用于增强药物输送的多糖衍生物

• 批准号: 1308276
• 负责人: Kevin Edgar
• 金额: $ 32.5万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1308276&HistoricalAwards=false
• 关键词: Collaborative; Research; Polysaccharide; Derivatives; Enhanced

The Biomaterials program in the Division of Materials Research funds the collaborative efforts of researchers at Purdue University and Virginia Polytechnic Institute to develop purpose-designed polymeric crystallization inhibitors to enhance drug solubility, and thereby enhancing the delivery of new drugs with improved therapeutic activity. Oral drug therapy is a key aspect of disease treatment, but many exciting new therapeutic agents fail because of poor water solubility. Such drugs do not reach adequate solution concentrations to be therapeutically effective. Using the amorphous form of the drug, which is a high energy form, can lead to much higher solution concentrations and higher levels of drug delivery to the body. The disadvantage of using amorphous formulations is that they are inherently unstable, frequently crystallizing during production, storage or delivery to the body, and thereby negating any solubility advantage. Although crystallization can be delayed or prevented by incorporating polymeric additives, the range of polymers with suitable properties is limited and the properties of off-the-shelf polymers properties are not optimal. The main aim of this project is to develop synthetic routes in producing novel orally biocompatible polysaccharide amphiphiles designed to inhibit solid and solution phase crystallization of drugs, and at the same time providing desired drug release profiles. Furthermore, the specific structural features governing drug-polymer intermolecular interaction and crystallization inhibition will be elucidated. The technological impact of the project is in creating improved delivery technologies for poorly water-soluble drugs, development of novel drug delivery processes and improved disease treatments. Increasingly, drug developers are interested in solubility enhancement strategies, and these researchers could benefit greatly from the fundamental understanding created by this research. Research findings will be integrated into teaching through undergraduate research activities involving underrepresented minority students, and development of new teaching materials based on this research.Providing patients with new and effective drugs, manufactured as tablets or capsules that can be taken orally, is a key aspect of treating chronic and acute diseases. Unfortunately, many of the new drugs currently being tested have poor solubility in water. The goal of this research is to improve the solubility of new drugs by combining them with novel polymers based on polysaccharides, which are natural, renewable, and abundant materials. These polymers will be synthesized and tested for their ability to improve the solubility and stability of drugs. By properly designing the polymer, it will interact with the drug and the solubility of the drug will be improved because the polymer will prevent it from crystallizing, and thus enhancing its solubility. This research will create improved delivery technologies for poorly water-soluble drugs, if the project is successful. Hence, this research could broadly improve disease treatment, and contribute to success of the drug development process. Research findings will be integrated into teaching through undergraduate research activities, and development of new teaching materials based on this project. Through summer undergraduate research programs at Purdue University and Virginia Tech, students will be recruited and mentored in research activities in the investigators' labs with the active participation of graduate students and faculty members.

材料研究部的生物材料计划为普渡大学和弗吉尼亚理工学院的研究人员合作提供资金，以开发专门设计的聚合物结晶抑制剂，以提高药物的溶解性，从而改善治疗活性的新药的输送。口腔药物治疗是疾病治疗的一个关键方面，但许多令人兴奋的新治疗药物因水溶性差而失败。这类药物没有达到足够的溶液浓度来发挥治疗效果。使用无定形形式的药物，这是一种高能形式，可以导致更高的溶液浓度和更高水平的药物输送到体内。使用无定形制剂的缺点是它们本质上不稳定，在生产、储存或输送到体内期间经常结晶，从而否定了任何溶解优势。虽然加入聚合物添加剂可以延缓或阻止结晶，但具有合适性能的聚合物范围有限，现成聚合物的性能也不是最优的。该项目的主要目的是开发合成路线，以生产新型口服生物相容的多糖两亲性药物，旨在抑制药物的固相和溶液结晶，同时提供所需的药物释放曲线。此外，还将阐明控制药物-聚合物分子间相互作用和结晶抑制的特殊结构特征。该项目的技术影响是为难于溶解的药物创造更好的给药技术，开发新的药物给药工艺和改进疾病治疗。越来越多的药物开发人员对溶解性增强策略感兴趣，这些研究人员可以从这项研究创造的基本理解中受益匪浅。研究成果将通过面向少数民族学生的本科研究活动整合到教学中，并在此研究的基础上开发新的教材。为患者提供新的有效药物，如片剂或胶囊，可口服，是治疗慢性和急性疾病的关键方面。不幸的是，目前正在测试的许多新药在水中的溶解性很差。本研究的目的是通过将新药与基于多糖的新型聚合物相结合来改善新药的溶解性，多糖是一种天然的、可再生的和丰富的材料。这些聚合物将被合成并测试它们改善药物的溶解性和稳定性的能力。通过适当的聚合物设计，它将与药物相互作用，药物的溶解性将得到改善，因为聚合物将阻止其结晶，从而提高其溶解性。如果该项目成功，这项研究将为难溶于水的药物创造更好的给药技术。因此，这项研究可以广泛地改善疾病的治疗，并为药物开发过程的成功做出贡献。研究成果将通过本科生研究活动和开发基于该项目的新教材来整合到教学中。通过普渡大学和弗吉尼亚理工大学的暑期本科生研究项目，将在研究生和教职员工的积极参与下，在调查实验室的研究活动中招募和指导学生。