目的 以双氯芬酸钠（ diclofenac sodium ， DS ）为模型药物，丝素蛋白（ silk fibroin ， SF ） / 壳聚糖 (chitosan ， CS)(1 ∶ 1) 为复合载体制备双氯芬酸钠丝素蛋白 / 壳聚糖缓释微球 (DS-SF/CS-MS) ，并考察其体内外相关性。 方法 采用乳化 - 化学交联固化法制备 DS-SF/CS-MS ；动态透析法考察了微球的体外释放特性；以 DS 溶液对照，大鼠分别 ig 相同剂量的 DS-CS-MS 和 DS-SF/CS-MS 后， HPLC 测定血浆中 DS 浓度， 3P97 程序计算药动学参数。 结果 DS-SF/CS-MS 的载药量和包封率分别为 (9.88±0.49)% 和 (50.35±0.92)% ，平均粒径为 (26.54±1.39) μm ； DS-SF/CS-MS 在不同 pH 的释放介质中均遵循 Higuchi 方程，其缓释效果明显优于双氯芬酸钠 - 壳聚糖微球 (DS-CS-MS) ；大鼠体内的双氯芬酸钠血药浓度经时曲线均符合一室模型， 3 种制剂的 MRT 分别为 (4.11±0.03) ， (6.92±0.39) 和 (24.35±0.27)h 。 DS-SF/CS-MS 的 MRT 与 <> t 1/2 明显延长，其相对生物利用度为溶液剂的 140.0% 。 结论 SF/CS-MS 的性能优异，有望成为一种低毒性的新型缓控释载体材料。
Abstract
OBJECTIVE To study preparation and pharmaceutical characteristics of diclofenac sodium loaded silk fibroin-chitosan microspheres(DS-SF/CS-MS) in vitro and in vitro. METHODS DS-SF/CS-MS were prepared with an emulsion crosslinking technique. Dynamic dialysis system was adopted to study the release dynamics of DS-SF/CS-MS in vitro. SD rats were used as the animal model. DS concentration in plasma was determined by HPLC after the intragastric administration of DS-CS-MS and DS-SF/CS-MS with same dose. Its pharmacokinetic parameters were calculated by 3P97 program. RESULTS The loading drug content and encapsulated efficiency of the microspheres were (9.88±0.49) % and (50.35±0.92)%, respectively. Its average diameter was about (26.54±1.39)μm. The release of DS-SF/CS-MS followed Higuchi's equation in PBS with different pH value. The slow-release property of DS-SF/CS-MS was better than that of the chitosan microspheres. The plasma concentration versus time curve was coincident with one compartment model. MRTs of the three formulation were (4.11±0.03), (6.92±0.39) and (24.35±0.27)h, respectively. Compared with DS solution and DS-CS-MS, t1/2 of DS-SF/CS-MS was prolonged and relative bioavailability was 140.0%. CONCLUSION SF/CS-MS was a potential novel sustained-release carrier material with low toxicity.
关键词
丝素蛋白 /
壳聚糖 /
缓释微球 /
双氯芬酸钠
{{custom_keyword}} /
Key words
silk fibroin /
chitosan /
controlled release microsphere /
diclofenac sodium
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LIU Y C, SHAO Z Z,SUN Y Y, et al. Structure and function of silk fibroin[J]. <>Polyme Bull ( 高分子通报 ), 1998(3): 17-23.
[2] ZHANG Y Q. Natural silk fibroin as a support for enzyme immobi-lization[J]. <>Biotechnol Adv, 1998, 16 (5-6): 961-971.
[3] ZHANG Y Q, ZHU J, SHEN W. Immobilization of glucose oxidase in silk fibroin membrances, their characteristics and application to biosisensor[J]. <>Suzhou Univ J( 苏州大学学报 ), 1997, 13(2):118-125.
[4] UNGER R E, MICHAEL W, KIRSTEN P, et al. Growth of human cells on a non2woven silk fibroin net: a potential for use in tissue en-gineering [J]. <>Biomatrials, 2004, 25(21): 1069-1075.
[5] ZUO B Q, WU H Y.Studies on the bio-degradable regenerated silk fibroin[J]. <>Silk( 丝绸 ), 2004, 11(10):14-18.
[6] FURUZONO T, TAGUCHI T, KISHIDA A, et al. Preparation and character-ization of apatited eposited on silk fabric using an alternate soaking p rocess [J]. <>J Biomed Mater Res, 2000, 50 (3): 344-352.
[7] ZHANG Y Z, DING Y, WU H Y. Release behavior of drug in composite fibroin membrane[J]. <>Silk( 丝绸 ), 2001, 8(3):10-11.
[8] ZHANG Y Z, WANG X F, HAN L L. Regenerated fibroin protein-preparation and structure of chitosan microcapsule[J]. <>Silk( 丝绸 ), 2002, 11(11): 17-21.
[9] <>Ch.P(2005)Vol Ⅱ ( 中国药典 2005 年版 . 二部 ) ［ S ］ . 2005:Appendix: 182-185.
[10] HOFMANN S, FOO C T, ROSSETTI F, et al. Silk fibroin as an organic polymer for controlled drug delivery [J]. J Controlled Release , 2006, 111(1-2):219-227.
[11] WANG X, WENK E, HU X, et al. Silk coatings on PLGA and alginate microspheres for protein delivery [J] . Biomaterials, 2007, 28(28): 4161-4169.
[12] SAVASER A, OZKAN Y, ISIMER A. Preparation and <>in vitro evaluation of sustained release tablet formulations of diclofenac sodium[J]. <>Farmaco, 2005, 60(2):171-177.
[13] JAMEELA S R, KUMARY T V, LAL A V, et al. Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system[J]. J Controlled Release, 1998, 52(1-2):17-24.
[14] MALAEKEH-NIKOUEI B, SAJADI TABASSI S A, JAAFARI M R. Preparation, characterization, and mucoadhesive properties of chitosan-coated microspheres encapsulated with cyclosporine A [J]. <>Drug Dev Ind Pharm, 2008, 34(5):492-498.
[15] WU C, PAN J, BAO Z, <>et al. Fabrication and characterization of chitosan microcarrier for hepatocyte culture[J] . <>Mater Sci Mater Med, 2007, 18(11):2211-2214.
[16] HINO T, TANIMOTO M, SHIMABAYASHI S. Change in secondary structure of silk fibroin during preparation of its microspheres by spray-drying and exposure to humid atmosphere [J]. <>Colloid Interface Sci, 2003, 266(1):68-73.
[17] CELIK O, AKBU ? A J. Preparation of superoxide dismutase loaded chitosan microspheres: characterization and release studies[J]. <>Pharm Biopharm, 2007, 66(1):42-47.
（ 收稿日期 ： 2008-12-05 ）
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(3615 KB)
