川陈皮素自组装前体脂质体制备及其大鼠体内药动学研究.docVIP

川陈皮素自组装前体脂质体的制备及其大鼠体内药动学研究 摘要： 本文研制川陈皮素自组装前体脂质体，并以混悬剂为对照考察其经大鼠灌胃给药后的药代动力学行为。采用一种新型前体脂质体法制备川陈皮素前体脂质体，考察其水合后粒径、包封率、稳定性等理化性质；大鼠分别灌胃给予川陈皮素混悬剂和水合后的脂质体后，以尼莫地平为内标，采用HPLC法测定血浆中药物浓度，用Kinatica4.4程序计算药动学参数。制得的脂质体包封率可达80%以上,平均粒径为212.1 nm，稳定性好；药代动力学研究显示,与混悬剂相比川陈皮素脂质体在体内吸收较快, 相对生物利用度264.3%，MRT增加。 结果表明，液态前体脂质体制备工艺简单，可行性高；川陈皮素制成前体脂质体后，大鼠口服吸收显著增加，并具有一定的缓释作用。 关键词：川陈皮素；自组装前体脂质体；药代动力学 Preparation of self-assemble nobiletin proliposomes and its pharmacokinetics in rats Abstract： To prepare self-assemble nobiletin proliposomes and study the pharmacokinetic behavior of nobiletin in rats after ig administration of nobiletin pro- liposomes and nobiletin suspension . Nobiletin proliposomes were prepared by a new kind of proliposome preparation method, the tests of physicochemical properties including encapsulation efficiency, particle size and stability of formed liposome were determined .Nobiletin suspension and nobiletin proliposmes were administrated to rats by ig administration, respectively. Plasma concentration of nobiletin was determined by HPLC taking nimodipine as internal standard. The pharmacokinetic parameters were calculated by Kinetica 4.4 software. The encapsulation efficiency of nobiletin liposomes was more than 80% , with an average particle size of 212.1 nm and very good stability. Compared to nobiletin suspension, nobiletin proliposomes possessed higher absorptive rate and longer MRT, and the relative bioavailability was 264.3% in rat. It could be concluded that nobiletin proliposomes was a simple and feasible preparation, and showed greater absorption and sustained-release characteristics compared with that of nobiletin. Key words: nobiletin; self-assemble proliposome; pharmacokinetics 川陈皮素(nobiletin，NOB)是从橘柑类植物中提取的多甲氧基黄酮类化合物，具有抗炎[1]、抗癌[2]等多种药理作用，抗癌作用表现为抗癌谱广，能预防癌症发生，防止肿瘤转移、复发，增强免疫力[2，3]等。目前国内外对川陈皮素的研究主要集中在药理方面，制剂学研究仅见有微乳报道[4]。川陈皮素脂溶性差且难溶于水，口服生物利用度低，脂质体作为新型的载体给药系统，具有生物膜特性和药物传输能力,将难溶性药物包裹在脂质双分子层中,使其具有较强的两亲性,可以显著提高药物的口服跨膜吸收及体内生物利用度[5]。本研究将川陈皮素制成口服给药的液态川陈皮素前体脂质体（nobiletin