Effects of Poly-L-arginine on the Permeation of Hydrophilic Compounds through Surface Ocular Tissues(Biopharmacy)
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概要
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We investigated whether poly-L-arginine (PLA) could improve permeation of the hydrophilic compounds, FITC-labeled dextran (MW 3800, FD-4) and pyridoxamine, through ocular surface tissues. Samples of cornea, conjunctiva, or conjunctiva/sclera composite from Japanese white rabbits were mounted in Ussing chambers to measure FD-4 and pyridoxamine permeation and transepithelial electric resistance (TEER). The integrity and viability of the conjunctiva were assessed by chronological TEER monitoring and MTT assay, respectively. The permeability coefficient (Papp) of FD-4 in the cornea, conjunctiva, and conjunctiva/sclera composite was increased by the addition of PLA (MW 38kDa, PLA (50)) at 0.1mg/ml by 6.81-, 9.78-, and 7.91-fold, respectively. The Papp of pyridoxamine was also increased in the presence of PLA (50) by 7.98-, 4.67-, 8.31-fold, respectively. A corresponding reduction in TEER was observed in all tissues. However, the reduced TEER in the case of the conjunctiva had recovered to ca. 70% 120min after replacing the mucosal fluid with fresh bicarbonated Ringer's solution. MTT assay results indicated that treatment of the conjunctiva with 0.1mg/ml PLA (50) did not change the production of formazan compared to that without PLA (50), indicating that the conjunctival viability is not significantly affected by PLA (50). Our findings suggest that PLA may be useful in promoting the ocular delivery of hydrophilic drugs without producing significant epithelial damage.
- 公益社団法人日本薬学会の論文
- 2006-01-01
著者
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KOBAYASHI Daisuke
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University
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UEDA Hideo
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University
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TAKAHASHI HIROKAZU
Department of Gastroenterology, Yokohama City University School of Medicine
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Ueda H
Faculty Of Pharmaceutical Sciences Josai University
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Kobayashi Daisuke
Department Of Biological Sciences Graduate School Of Science University Of Tokyo
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Kobayashi D
Fac. Of Pharmaceutical Sciences Josai Univ.
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Ueda H
Kyoto Pharmaceutical University
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森本 泰子
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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Morimoto Y
Josai Univ. Saitama Jpn
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Morimoto Y
Faculty Of Pharmaceutical Sciences Josai University:research Institute Of Tts Technology
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Morimoto Yasunori
Fac. Of Pharmaceutical Sciences Josai Univ.
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Morimoto Yasunori
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Josai University
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Ueda H
Hoshi Univ. Tokyo Jpn
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Ueda H
Department Of Physical Chemistry Hoshi University
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Ueda H
Faculty Of Pharmaceutical Sciences Hoshi University
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Ueda Haruhisa
Research Institute For Scientific Measurements Tohoku University
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Ueda Haruhisa
Faculty Of Pharmaceutical Science Hoshi University
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Ueda Hideo
Fac. Of Pharmaceutical Sciences Josai Univ.
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NEMOTO Eiichi
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University
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Nemoto Eiichi
Faculty Of Pharmaceutical Sciences Josai University:faculty Of Pharmaceutical Science Josai Internat
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Nemoto Eiichi
Faculty Of Pharmaceutical Science Josai International University
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Morimoto Yasunori
Faculty Of Pharmaceutical Sciences Josai University:research Institute Of Tts Technology
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Ueda H
Fac. Of Pharmaceutical Sciences Josai Univ.
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上田 仁司
Kawanishi Pharma Research Institute Nippon Boehringer Ingelheim Co. Ltd.
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Kobayashi Daisuke
Fac. Of Pharmaceutical Sciences Josai Univ.
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Kobayashi Daisuke
Department Of Applied Chemistry Faculty Of Science And Technology Keio University
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Ueda Hideo
Department Of Computer Science And Electronics Kyushu Institute Of Technology
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Takahashi Hirokazu
Lab. Of Clinical Pharmaceutics Fac. Of Pharmaceutical Sciences Kobe Gakuin Univ.
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Takahashi Hirokazu
Department Of Electrical Engineering Faculty Of Engineering Nagaoka University Of Technology
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TAKAHASHI Hirokazu
Department of Agricultural Chemistry, Faculty of Agriculture, Tohoku University
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