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.
