Collaborative Research: Polysaccharide Derivatives for Enhanced Drug Delivery

材料研究部的生物材料项目资助了普渡大学和弗吉尼亚理工学院的研究人员的合作努力，以开发专门设计的聚合物结晶抑制剂，以提高药物的溶解度，从而增强新药的输送，提高治疗活性。口服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由于水溶性差而失败。这类药物的溶液浓度不足以达到治疗效果。使用药物的无定形形式，这是一种高能量形式，可以导致更高的溶液浓度和更高水平的药物输送到体内。使用非晶态制剂的缺点是它们本身不稳定，在生产、储存或输送到体内时经常结晶，从而否定了任何溶解度优势。虽然可以通过加入聚合物添加剂来延缓或阻止结晶，但具有合适性能的聚合物的范围是有限的，而且现成聚合物的性能也不是最佳的。本项目的主要目的是开发合成路线，以生产新的口服生物相容性多糖两亲体，旨在抑制药物的固相和固相结晶，同时提供所需的药物释放谱。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具体结构特征。该项目的技术影响在于为水溶性差的药物创造改进的输送技术、开发新的药物输送工艺和改进疾病治疗。越来越多的药物开发人员对溶解度增强策略感兴趣，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。研究成果将通过涉及代表性不足的少数民族学生的本科生研究活动，并在此基础上开发新的教材，融入教学。为患者提供可口服的片剂或胶囊形式的新型有效药物，是治疗慢性和急性疾病的一个关键方面。不幸的是，目前正在测试的许多新药在水中的溶解度很差。本研究的目的是通过将新药与天然、可再生、储量丰富的多糖为基础的新型聚合物结合，提高新药的溶解度。这些聚合物将被合成并测试其改善药物溶解度和稳定性的能力。通过适当的设计聚合物，它将与药物相互作用，提高药物的溶解度，因为聚合物可以防止药物结晶，从而提高其溶解度。如果该项目成功，这项研究将为水溶性差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治疗，并有助于药物开发过程的成功。研究成果将通过本科生的研究活动和基于本项目的新教材的开发融入教学。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，学生们将被招募并在研究人员实验室的研究活动中得到指导，研究生和教职员工将积极参与。

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.