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Preparation of Hydrogen Bonding Polymer Structures Using Ultra High Pressure Technology as Drug Carrier

Yoshiyuki Miura1, Kimio Kurita1, Kwangwoo Nam2, Shingo Mutsuo3, Hidekazu Yoshizawa3, Toshiya Fujisato4, Tsuyoshi Kimura2, and Akio Kishida2. (1) Department of Materials and Applied Chemistry, Nihon University, 1-8-14 Kanda-Surugadai, Chiyoda-ku, Tokyo, Japan, (2) Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku,, Tokyo, Japan, (3) Department of Material and Energy Science, Okayama University, Okayama, Japan, (4) National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Japan

Molecular assembling technology is of important for drug delivery system. Previously, many researchers have studied the molecular assembly by various interactions such as using van der Waals interaction, electrostatic interaction and hydrogen bonding. In this study, we performed the preparation of hydrogen bonding polymer structures as drug carrier using ultra high pressure (UHP) technology, which emphasize hydrogen bonding interaction between molecules. Various hydrogen bonding polymers, such as poly(vinyl alcohol)(PVA), poly(ethylene glycol)(PEG), dextran and pullulan, were used. These solutions at different concentrations were prepared and pressed under at 980MPa (10000 atm) at 25 degree (UHP treatment). In the case of PVA, the formation of nano-particles was observed by SEM observation. On the other hand, the clear solutions were maintained using PEG, dextran and pullulan after UHP treatment. However, when PEG (Mw: 6,000 or 8,000) were mixed with DEX (Mw:60,000-90,000) or pullulan, the solution with light scattering was obtained. After UHP treatment, aqueous two-phase separation having light scattering in lower phase was obtained for all cases, suggesting that apparent molecular weight was increased by the formation of PEG/ polysaccharides complex. DLS measurement of them before/after UHP treatment was carried out. The particle size was increased by UHP treatment, then decreased by heat treatment at 50 degrees, indicating the formation of novel hydrogen bonding structures. These results indicate the utility of UHP technology for molecular assembly.