Formation of cycloextrin - drug inclusion complexes and scaffolds with the aid of supercritical fluids

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0929978KiranThis is a research program on exploration of novel methodologies that aim at using supercritical fluids to form drug inclusion complexes with cyclodextrins, as well as forming polymer matrices or scaffolds that are embedded with drug-cyclodextrin complexes. Supercritical fluids are tunable fluids that can reduce or eliminate the use of organic solvents in synthesis, purification, and post-processing of biopolymers and drugs to generate particles, membranes or scaffolds that can be used in drug delivery or other medical devices. For drug delivery, particle size, shape, morphology and crystal form of the drug molecules are very important as they influence the rate of dissolution and the release characteristics of drugs. For scaffolds, porosity along with built-in drug-release features that incorporate anti-inflammatory drugs and/ or growth factors are important factors that ensure transport of nutrients, promotion of cell proliferation, and prevention of infections during organ regeneration. Cyclodextrins have hydrophobic internal cavities in which drug molecules can be incorporated as guest molecules. A unique aspect of this research is the exploration of development of novel drug-cyclodextrin complexes using polymeric forms of cyclodextrins, such as polymers with pendant cyclodextrin groups, which can be formed and directly transformed into porous scaffolds in supercritical fluid media. Formation of drug-cyclodextrin inclusion complexes within a biodegradable polymer matrix such as poly(å-caprolactone) is another novel aspect that aims at generation of tissue engineering scaffolds with a built-in and/or improved drug delivery feature. Dual drug delivery systems that combine drug-cyclodextrin matrices along with a growth factor embedded in biodegradable polymer matrices are being considered to generate novel scaffolds that incorporate in-situ drugs to minimize inflammation and in-situ growth factors that are critical in promoting organ regeneration.The research involves fundamental studies on miscibility and phase separation in multicomponent systems involving small (drug) and large (polymeric) molecules and supercritical fluid mixtures (carbon dioxide + cosolvent) to understand the overall thermodynamics, and the nano-scale dynamics of guest-host interactions involving drug molecules, cyclic compounds and polymers with cavities that can form inclusion complexes. Studies are directed to understanding the consequences of processing in supercritical fluid media in terms of morphology, crystallinity, and polymorphism as well as documentation of drug release dynamics from such multi-component matrices.The research program brings together the expertise of the PI in supercritical fluids and polymers with the expertise of the co-PI in natural polymer-based drug release and cellular engineering systems. The interdisciplinary nature of the program is expected to have a broad impact in a wide range of other application areas from polymers to sensors, and create broad educational opportunities to graduate and undergraduate students with different diversity, gender and backgrounds.