Surface Modification of RGD-Liposomes for Selective Drug Delivery to Monocytes/Neutrophils in Brain
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概要
- 論文の詳細を見る
In the present study, RGD peptide was coupled with ferulic acid (FA) liposomes for binding to monocytes and neutrophils in peripheral blood for brain targeting in response to leukocyte recruitment. Cholesterol (Ch) was esterified with succinic anhydride to introduce a carboxylic end group (Ch-COOH). Soybean phosphatidyl-choline, cholesterol and Ch-COOH were in a molar ratio of 1:0.23:0.05. FA was loaded into liposomes with 80.2±5.2% entrapment efficiency (EE) using a calcium acetate gradient method since it was difficult to load FA by other methods. RGD peptide was a novel compound coupled with Ch-COOH via carbodiimide and N-hydroxysulfosuccinimide. The results of the in vitro flow cytometric study showed that RGD conjugation liposomes (RGD-liposomes) could bind to monocytes/neutrophils efficiently. The rats were subjected to intrastriatal microinjections of 100μl of human recombinant IL-1μ to produce brain inflammation and subsequently sacrificed after 15, 30, 60 and 120 min of administration of three formulations (FA solution, FA liposome, RGD-coated FA liposome). The body distribution results showed that RGD-liposomes could be directed to the target site, i.e. the brain, by cell selectivity in case of an inflammatory response. For RGD coated liposomes, the concentration of FA in brain was 6-fold higher than that of FA solution and 3-fold higher than that of uncoated liposomes. MTT assay and flow cytometry were used in the pharmacodynamic studies where it was found that FA liposomes exhibited greater antioxidant activity to FA solution on U937 cell.
- 公益社団法人日本薬学会の論文
- 2007-08-01
著者
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CHEN Dawei
Department of Pharmaceutics, Shenyang Pharmaceutical University
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CUI Qiao
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical Universit
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QIN Jing
Department of Mechanical Systems Engineering, Tokyo University of Agriculture and Technology
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Cui Qiao
China-japan Institute Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical University
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Qiao Mingxi
Department Of Pharmaceutics School Of Pharmacy Shenyang Pharmaceutical University
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Qin Jing
Department Of Pharmaceutics School Of Pharmacy Shenyang Pharmaceutical University
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Chen Dawei
School Of Pharmacy Shenyang Pharmaceutical Univ.
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HU HaiYang
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University
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CHEN Bao
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University
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Chen Bao
Department Of Pharmaceutics School Of Pharmacy Shenyang Pharmaceutical University
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Cui Qiao
China-japan Research Institute Of Medical Pharmaceutical Sciences Shenyang Pharmaceutical University
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Qin Jing
Department Of Mechanical Systems Engineering Tokyo University Of Agriculture And Technology
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Chen Dawei
Department Of Biopharmaceutics School Of Pharmacy Shenyang Pharmaceutical University
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