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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/27672

    標題: Combined strategies of apomorphine diester prodrugs and nanostructured lipid carriers for efficient brain targeting
    作者: Liu, Kuo-Sheng
    Wen, Chih-Jen
    Yen, Tzu-Chen
    Sung, K.C.
    Ku, Ming-Chuan
    Wang, Jhi-Joung
    Fang, Jia-You
    貢獻者: 藥學系
    關鍵字: Central-Nervous-System
    日期: 2012-03-09
    上傳時間: 2014-03-21 16:17:11 (UTC+8)
    出版者: Iop Publishing Ltd
    摘要: Our aim is to develop nanostructured lipid carriers (NLCs) for loading the apomorphine diester prodrugs, diacetyl apomorphine (DAA) and diisobutyryl apomorphine (DIA), into the brain. NLCs were prepared using sesame oil/cetyl palmitate as the lipid matrices. Experiments were performed with the objective of evaluating the physicochemical characteristics, drug release, safety and brain-targeting efficacy of the NLCs. The size of regular NLCs (N-NLCs) was 214 nm. The addition of Forestall (FE) and polyethylene glycol (PEG) to the NLCs (P-NLCs) increased the particle diameter to 250 nm. The zeta potentials of N-NLCs and P-NLCs were respectively shown to be -21 and 48 mV. Diester prodrugs were more lipophilic and more chemically stable than the parent apomorphine. The hydrolysis study indicated that the prodrugs underwent bioconversion in plasma and brain extract, with DAA exhibiting faster degradation than DIA. Sustained release was achieved through the synergistic effect of integrating strategies of prodrugs and NLCs, with the longer carbon chain showing the slower release (DIA < DAA). None of the NLCs tested here exhibited a toxicity problem according to the examination of neutrophil lactate dehydrogenase (LDH) release and hemolysis. Results of a bioimaging study in mice showed that P-NLCs largely accumulated in the brain. The distribution duration of the fluorescent dye in the brain region was also prolonged by the nanocarriers.
    Appears in Collections:[藥學系(所)] 期刊論文

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