438653 Simple, Novel and Applicable Strategies for Innovative Medical Solutions

Sunday, November 8, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Shiyi Zhang, MIT, Cambridge, MA, Robert Langer, Koch Institute for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA and Karen L. Wooley, Department of Chemistry, Texas A&M University, College Station, TX

During my PhD research in Prof. Karen Wooley’s laboratory, my interests ranged from degradable polyphosphoester-based nanomaterials for nanomedicine to the self-assembly of block copolymers for complex functional nanostructures. The development of synthetic methodologies for the preparation of complex, functional polymer materials by simple strategies has enormous potential for biological applications.  My past research on the polyphosphoester-based nanomaterials has built a platform that enables a rapid and versatile construction of two families of degradable nanoparticles in treating diseases, such as pulmonary cancers, infections and injuries. Two degradable nanoparticle systems based on one alkyne-functionalized polyphosphoester and their broad applicability, will be discussed.  The highly water soluble backbone of the polyphosphoester endowed the first system with ultrahigh paclitaxel loading capacity (55 wt%) and a maximum paclitaxel concentration of 6.2 mg/mL in water, for the treatment of lung cancers.  In the second system, the easily functionalizable side-chain of the polyphosphoester allowed us to prepare a family of nanoparticles with diverse surface charge types, non-ionic, anionic, cationic and zwitterionic, in a rapid and versatile manner.  The anionic nanoparticles are designed to load silver ions to treat pulmonary infections, while the cationic nanoparticles are being applied to regulate lung injuries by their degradation products.

My postdoc research in Prof. Bob Langer’s laboratory is focusing on the development of  novel technologies for prolonged gastric residence time and in turn extended release of loaded drugs, potentially to facilitate the oral administration on an infrequent - potentially even a one-time - basis in order to maximize medication adherence. Devices resident in the stomach - which are used for a variety of clinical applications including nutritional modulation for bariatrics, ingestible electronics for diagnosis and monitoring, and gastric-retentive dosage forms for prolonged drug delivery - typically incorporate elastic polymers to compress the devices during delivery through the oesophagus and other narrow orifices in the digestive system.  However, in the event of accidental device fracture or migration, the non-degradable nature of these materials risks intestinal obstruction.  Here, we show that an elastic, pH-responsive supramolecular gel remains stable and elastic in the acidic environment of the stomach but can be dissolved in the neutral-pH environment of the small and large intestines.  In a large animal model, prototype devices with these materials as the key component demonstrated prolonged gastric retention and safe passage.  These enteric elastomers should increase the safety profile for a wide range of gastric-retentive devices.  We have been working on loading various drugs into such gastric device for the extended release to solve the poor medication adherence problem.  

My PhD and postdoc research utilized different polymeric materials for distinct applications, but shared the same design principle that is simple, novel and applicable.

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