Polymer micelle stabiity as examined by Förster resonance energy transfer.
Polymer micelle stabiity as examined by Förster resonance energy transfer. |
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The goal of this research is to develop clinically effective polymer micelle systems for cancer therapy. Polymer micelles have been widely used for delivery of hydrophobic drugs into cells and tumors. Despite the extensive use of polymer micelles, the mechanisms underlying cellular uptake of polymer micelles as well as stability in the blood are not clearly understood. These make it difficult to develop effective polymer micelle systems. The stability of polymer micelles in blood appears to be prerequisite for successful tumor therapy. Only the stable polymer micelles may have chances to reach the target tumors and deliver anti-tumoral drugs at the therapeutically effective level.
The specific aims of this project are: to develop adaptable polymer micelles; to examine their stability in blood; to elucidate the micelle-tumor cell interactions; and to characterize the in vivo fate of micelles and to study the anti-tumoral activity of drug-loaded micelles.
(More information on the project will be added in the near future. In the meantime, the background information can be found in the following articles dealing with polymer micelles.)
Chen, H., Kim, S., Li, L., Wang, S., Park, K., Cheng, J-X.: Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Förster resonance energy transfer imaging, Proc. Natl. Acad. Sci. USA, 105 (18): 6596-6601, 2008.
Chen, H., Kim, S., He, W., Wang, H., Low, P.S., Park, K., and Cheng, J-X.: Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo Förster resonance energy transfer imaging, Langmuir, 24: 5213-5217, 2008.
Kim, S., Kim, J-H., Jeon, O., Kwon, I.C., Park, K.: Engineered polymers for advanced drug delivery, Eur. J. Pharm. Biopharm., 71: 420-430, 2009.
Kim, S.W., Shi, Y., Kim, J.Y., Park, K., and Cheng, J.X.: Overcoming the barriers in micellar drug delivery: Loading efficiency, in vivo stability, and micelle-cell interaction, Expert Opinion on Drug Delivery, in press.
Shi, Y., Kim, S.W., Huff, T.B., Borgens, R.B., Park, K., Shi, R., and Cheng, J.-X.: Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles, Nature Nanotech, in press. doi:10.1038/nnano.2009.303.
Lee, J., Acharya, G., Lee, S.C., and Park, K.: Hydrotropic solubilization of paclitaxel: Analysis of chemical structures for hydrotropic property, Pharm. Res., 20: 1022-1030, 2003.
Lee, S.C., Acharya, G., Lee, J., and Park, K.: Hydrotropic polymers: Synthesis and characterization of polymers containing picolylnicotinamide moieties, Macromolecules, 36: 2248-2255, 2003.
Ooya, T., Lee, J., and Park, K.: Effects of ethylene glycol-based graft, star-shaped, and dendritic polymers on solubilization and controlled release of paclitaxel, J. Control. Release, 93: 121-127, 2003.
Cho, Y.W., Lee, J., Lee, S.C., Huh, K.M., and Park, K.: Hydrotropic agents for study of in vitro paclitaxel release from polymeric micelles, J. Control. Release, 97: 249-257, 2004.
Ooya, T., Lee, J., and Park, K.: Hydrotropic dendrimers of generations 4 and 5: Synthesis, characterization, and hydrotropic solubilization of paclitaxel, Bioconjugate Chem., 15: 1221-1229, 2004.
Ooya, T., Huh, K.M., Saitoh, M., Tamiya, E., and Park, K.: Self-assembly of cholesterol-hydrotropic dendrimer conjugates into micelle-like structure: Preparation and hydrotropic solubilization of paclitaxel, Science and Technology of Advanced Materials, 6: 452-456, 2005.
Lee, S.C., Huh, K.M., Lee, J., Cho, Y.W., Galinsky, R.E., and Park, K.: Hydrotropic polymeric micelles for enhanced paclitaxel solubility: In vitro and in vivo characterization, Biomacromolecules, 8: 202-208, 2007.
Min, H.S., Lee, H.J., Lee, S.C., Kang, K.H., Lee, J., Park, K., and Huh, K.M.: Aqueous solubilization of paclitaxel using hydrotropic polymer micelle, Key Engineering Materials, 342-343: 421-424, 2007.
Huh, K.M., Mi, H.S., Lee, S.C., Lee, H.J., Kim, S., Park, K.: A new hydrotropic block copolymer micelle system for aqueous solubilization of paclitaxel, J. Control. Release, 126: 122-129, 2008.
Kim, S. Kim, J.Y., Huh, K.M., Acharya, G., and Park, K.: Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel. J. Control. Release 132, 222-229, 2008.
Saravanakumar, G., Min, H.H., Min, D.S., Kim, A.Y., Lee, C.M., Cho, Y.W., Lee, S.C., Kim, K., Jeong, S.Y., Park, K., Park, J., and Kwon, I.C.: Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paxclitaxel: Synthesis, characterization, and in vivo biodistribution, J. Control. Release, 140: 210-217, 2009.
Huh, K.M. and Park, K.: Copolymer, block copolymers stimuli and thermosensitive polymers, in Biomaterials-based Delivery and Biocompatibility of Protein and Nucleic Acids, Mahato, R., Ed., CRC Press, 2005, pp. 73-93.
Ooya, T. and Park, K.: Polymer solution properties, micelles, dendrimers, and hydrogels, in Biomaterials-based Delivery and Biocompatibility of Protein and Nucleic Acids, Mahato, R., Ed., CRC Press, 2005, pp. 95-118.
Huh, K., Lee, S.C., Ooya, T., and Park, K.: Polymeric delivery systems for poorly soluble drugs, in Encyclopedia of Pharmaceutical Technology, 2nd Edn. Swarbrick, J., Ed., Marcel Dekker, New York, NY, 2004.
Ooya, T., Lee, S.C., Huh, K.M., and Park, K.: Hydrtropic nanocarriers for poorly soluble drugs, in Nano-encapsulation Technologies: Frontiers of Nanotherapy, Mozafari, R., Ed., Springer, Netherlands, 2006, Vol. 1, pp. 51-73.
S. C. Lee, K. M. Huh, T. Ooya, and K. Park: Hydrotropic Polymer Micelles for Cancer Therapeutics, in Nanotechnology for Cancer Therapeutics, Amiji, M., Ed., CRC Press, 2007, pp. 385-408.
Kim, S.W. and Park, K.: Polymer micelles for drug delivery, in Targeted Delivery of Small and Macromolecular Drugs: Problems Faced and Approaches Taken, Ajit Narang and Ram Mahato, Eds., Taylor and Francis Group, in press.