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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, Silk-elastinlike protein polymers for matrix-mediated cancer gene therapy, Advanced Drug Delivery Reviews, Vol. 62, No. 15, pp. 1509-1523, 2010].
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 are being investigated. By tailor-making the size and charge of these copolymers it is possible to alter biodistribution and minimize uptake by nontarget organs. Similar polymeric systems have been evaluated for targeted delivery of antileishmanial and magnetic resonance contrast agents. For a recent article see [D. Pike, H. Ghandehari, HPMA copolymer-cyclic RGD conjugates for tumor targeting, Advanced Drug Delivery Reviews, Vol. 62, No. 2, pp. 167-183, 2010].
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 and charge can be transported across the gastrointestinal epithelial cells with minimal or no toxicity. The influence of variables such as size, geometry, charge, surface functionality and drug loading on the mechanism and rate of transport of PAMAM dendrimers across epithelial barriers is under investigation. For a recent article see [D.S. Goldberg, H. Ghandehari, P.W. Swaan, Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia, Pharmaceutical Research, Vol. 8, pp. 1547-1557, 2010].
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 [Arnida, M.M. Janat-Amsbury, A. Ray, C.M. Peterson, H. Ghandehari, Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages, European Journal of Pharmaceutics and Biopharmaceutics, Vol. 77, No. 3, pp. 417-23, 2011; and H.L. Herd, A. Malugin, H. Ghandehari, Silica nanoconstruct cellular toleration threshold in vitro, Journal of Controlled Release, Article in Press, Corrected Proof, 2011]. In another effort we are working on constructing inorganic-polymer hybrid nanoconstructs responsive to external stimuli for controlled chemical delivery