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The main focus of research in our laboratory is the development of novel methods for controlled delivery of bioactive agents. Four areas are being explored:
Recombinant DNA technology has enabled the synthesis of protein-based polymers with precisely controlled structures. Control over polymer structure at the molecular level has important implications for controlled delivery applications. The potential of recombinant silk-elastinlike protein polymers (SELPs) for matrix-mediated gene delivery is being explored. The idea is that by using recombinant techniques it is possible to systematically correlate polymer structure with gene release and transfer. Our main focus is on gene therapy applications in the treatment of head and neck cancer. For a recent article see [J.Gustafson, H. Ghandehari, Advanced Drug Delivery Reviews, 62:1509-1523, 2010]. More recent efforts focus on design of recombinant polymers with sequences responsive to matrix-metalloproteinases [J. Gustafson, R. Price, J. Frandsen, C.R. Henak, J. Cappello, and H. Ghandehari, Biomacromolecules, 14:618-625, 2013].
Targeted delivery of bioactive agents by water soluble polymers can increase efficacy and reduce toxicity. The synthesis, characterization and biological evaluation of targetable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers for targeted delivery to angiogenic blood vessels of solid tumors have been investigated [D. Pike, H. Ghandehari, Advanced Drug Delivery Reviews, 62:167-183, 2010]. More recent efforts focus on gold nanorod-mediated hyperthermia for enhanced delivery of macromolecular therapeutics to solid tumors [A.J. Gormley, N. Larson, S. Sadekar, R. Roinson, A. Ray, and H. Ghandehari, Nano Today, 7:158-167, 2012; N. Larson, A. Gormley, N. Frazier, and H. Ghandehari, Journal of Controlled Release, 170:41-50, 2013].
Due to their large size water soluble polymers generally need to be administered intravenously. It would be desirable to develop polymeric carriers that are orally bioavailable. Nano-scale poly(amidoamine) (PAMAM) dendrimers of appropriate size, charge and concentration can be transported across the gastrointestinal epithelial cells with minimal or no toxicity. The influence of variables such as size, charge, surface functionality and drug loading on the mechanism and rate of transport of PAMAM dendrimers across epithelial barriers has been investigated. More recent efforts focus on in vivo oral bioavailability of PAMAM dendrimers and their transepithelial transport across isolated intestinal tissue. For a recent article on this topic see [S. Sadekar and H. Ghandehari, Advanced Drug Delivery Reviews, 64:571-88, 2012].
Recent advances in nanotechnology have enabled the fabrication of inorganic nanoconstructs with defined shape, size, and surface functionality. Examples of such constructs include inorganic nanorods and nanospheres. Efforts are directed at evaluating the influence of geometry and surface functionality on biocompatibility and biodistribution of silica and gold nanoparticles, as well as poly(amido amine) dendrimers. For recent articles see [K. Greish, G. Thiagarajan, H. Herd, R. Price, H. Bauer, D. Hubbard, A. Burckle, S. Sadekar, T. Yu, A. Anwar, A. Ray, and H. Ghandehari, Nanotoxicology, 6:713-723, 2012; T. Yu, K. Greish, L. McGill, A. Ray, and H. Ghandehari, ACS Nano, 6:2289-2301, 2012; H. Herd, N. Daum, A. Jones, H. Huwer, H. Ghandehari, and C.M. Lehr, ACS Nano, 7:1961-1973, 2013].