Preparation and Characterization of Insulin-Loaded Acrylic Hydrogels Containing Absorption Enhancers

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概要

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• The objectives of this study were to prepare insulin-loaded acrylic hydrogel formulations containing various absorption enhancers, to perform in vitro and in vivo characterization of these formulations, and to evaluate the factors which affecting insulin availability on rectal delivery of insulin using this hydrogel system. The acrylic block copolymer of methacrylic acid and methacrylate, Eudispert^<(R)> was used to make the hydrogel formulations. As absorption enhancers, 2, 6-di-O-methyl-β-cyclodextrin(DM-β-CyD), lauric acid(C12), or the sodium salt of C12(C12Na), were incorporated into the hydrogels. In an in vitro release test, the release rate of insulin from the hydrogels decreased as the polymer concentration of the hydrogel increased. The addition of C12Na to the hydrogel further increased the insulin release rate, which was greater at higher concentrations of the enhancer. A portion of the C12Na was found to remain bound to the acrylic polymer in dissolution medium. Serum insulin levels were determined at various time points after the administration of insulin solution or insulin-loaded(50 units/kg body weight)Eudispert^<(R)> hydrogels containing 5%(w/w)of C12, C12Na, or DM-β-CyD to in situ loops in various regions of the rat intestine. The most effective enhancement of insulin release was observed with formulations containing C12Na. The bioavailability of insulin from the hydrogels was lower than that from the insulin solutions. Hydrogel formulations containing 7% or 10% Eudispert^<(R)> remained in the rectum for 5h after rectal administration. However, the 5%(w/w)C12Na solution stained with Evan's-blue had diffused out and the dye had reached the upper intestinal tract within 2h. Finally, the rectal administration of insulin-loaded hydrogels, containing 4%, 7%, or 10%(w/w)Eudispert^<(R)> and 5%(w/w)of enhancer(C12, C12Na, or DM-β-CyD)to normal rats was shown to decrease serum glucose concentrations. The greatest effect was found with insulin-loaded 7%(Eudispert^<(R)>)hydrogel containing C12Na which having cosiderable large insulin release rate and bioadhesive characteristics.

• 公益社団法人日本薬学会の論文
• 2001-10-01

著者

• Tanaka H

  Faculty Of Pharmacy Meijo University

• Miyanaga Y

  School Of Pharmaceutical Sciences Mukogawa Women's University

• Miyanaga Yohko

  School Of Pharmaceutical Sciences Mukogawa Women's University

• Tanaka H

  Department Of Agricultural Chemistry Faculty Of Agriculture Utsunomiya University

• Tanaka H

  Department Of Bioresources Chemistry Faculty Of Agriculture Okayama University

• Tanaka H

  Exploratory Research Laboratories Fujisawa Pharmaceutical Co. Ltd.

• YASUDA Noriko

  Faculty of Pharmaceutical Sciences, Mukogawa Womens University

• MATSUYAMA KENJI

  Faculty of Pharmaceutical Sciences, Kyushu University

• Matsuyama Kenji

  Faculty Of Pharmaceutical Sciences Kyushu University

• Matsuyama Kenji

  School Of Pharmaceutical Sciences Mukogawa Women's University

• Matsuyama Kenji

  Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Mukogawa Women's University

• Toyama Hirohide

  Institute For Chemical Research Kyoto University

• Tanaka Haruyuki

  Chemical Branch Faculty Of Engineering And Kansai University High Technology Research Center Kansai

• Nishikata Mayumi

  Faculty Of Pharmaceutical Sciences Mukogawa Women's University

• UCHIDA Takahiro

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

• TOIDA Yuka

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

• SAKAKIBARA Sadako

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

• MIYANAGA Yohko

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

• TANAKA Hiromi

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

• TAZUYA Keiko

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

• Tanaka K

  Laboratory Of Animal Science Kyoto Prefectural University

• Tanaka Hiroyoki

  Faculty Of Pharmaceutical Sciences Kyushu University

• Toida Yuka

  Faculty Of Pharmaceutical Sciences Mukogawa Women's University

• Nishikata M

  School Of Pharmaceutical Sciences Mukogawa Women's University

• Tazuya Keiko

  Faculty Of Pharmaceutical Sciences Mukogawa Women's University

• Yasuda N

  Faculty Of Pharmaceutical Sciences Mukogawa Women's University

• Yasuda Noriko

  Faculty Of Pharmaceutical Sciences Mukogawa Women's University

• Uchida Takahiro

  Faculty Of Pharmaceutical Sciences Kyushu University

• Tanaka Hiromi

  Faculty Of Bioresources Mie University

• TANAKA Hiromi

  Department of Physics Faculty of Education, Saga University

• Sakakibara Sadako

  Faculty of Pharmaceutical Sciences, Mukogawa Women's University

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