Preparation of the etoposide chitosan micelle and the effect of chitosan on etoposide intestinal absorption
-
摘要: 目的 制备依托泊苷壳聚糖胶束，并研究壳聚糖对依托泊苷肠吸收的促进作用。 方法 用透析法制备依托泊苷壳聚糖胶束，建立依托泊苷HPLC含量测定方法，测定了其包封率与载药量；采用大鼠在体肠循环实验，研究不同剂量壳聚糖对依托泊苷全肠段和各个肠段吸收的影响。 结果 壳聚糖胶束平均粒径为139.5 nm，多分散系数为0.569；依托泊苷标准曲线为A=8 436.8C-4 963.8，r=1.000 0，日内、日间精密度符合要求；包封率为（47.3±2.84）%，载药量为（1.10±1.27）%；随着壳聚糖浓度的增加，依托泊苷在全肠段的单位面积吸收量有不同程度的增加；壳聚糖对依托泊苷的吸收促进作用存在着肠道特异性，作用大小顺序：回肠 >空肠 >十二指肠。 结论 在十二指肠、空肠和回肠，壳聚糖都不同程度促进了药物的吸收，且在空肠和回肠有显著性的影响。Abstract: Objective To prepare the etoposide chitosan micelle, and investigate the effect of chitosan on etoposide intestinal absorption. Methods The etoposide chitosan micelle was prepared by dialysis. The drug encapsulation efficiency and drug loading efficiency were determined by HPLC. The intestine in rats was cannulated for in situ recirculation. The effects of different chitosan doses on the intestinal drug absorption and the effects of chitosan on the drug absorption at different intestinal locations were studied. Results The average particle size of etoposide chitosan micelle was 139.5 nm. The multi-dispersion coefficient was 0.569. The standard curve of etoposide was A = 8 436.8 C-4 963.8,r=1.000 0. The intra-and inter-day precision values meetthe requirement. The drug encapsulation efficiency was (47.3±2.84)% and drug loading efficiency was (1.10±1.27)%. With the increase of the chitosan concentration, the absorption capacity of the unit area in the whole intestine was increased in different degrees. Chitosan exhibits its effects on etoposide absorptionat different intestinal sections in the following order: ileum >jejunum >duodenum. Conclusion Chitosan promoted etoposide absorption induodenum, jejunum and ileum, especially in jejunum and ileum.
-
Key words:
- chitosan /
- etoposide /
- intestinal absorption
-
[1] Li M, Si L, Pan H, et al. Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition: assessed in vitro by everted gut sac and in situ by improved intestinal perfusion [J]. Int J Pharm, 2011, 403(1-2):37-45. [2] Choo E, Leake B, Wandel C, et al. Pharmacological inhibition of P-GP transport enhances the distribution of HIV-1 protease inhibitors into brain and testes[J]. Drug Metab Dispos, 2000, 28(6): 655-660. [3] Illum L.Chitosan and its use as a pharmaceutical excipient[J].Pharm Res,1998,15(9): 1326-1331. [4] Kotze AR,Lueben HL,Leeuw BJD,et al.N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surface:in vitro evaluation in intestinal epithelial cells(Caco-2)[J].Pharm Res,1997,14(9):1197-1202. [5] 姚 静,卢 韵,周建平,等. 川陈皮素自微乳的制备及其大鼠在体肠吸收动力学[J]. 中国药科大学学报,2007,38(1):35-38. [6] 袁 泉,李馨儒,王会娟,等. 水飞蓟素微乳大鼠在体小肠吸收的动力学[J]. 药学学报,2004,39(8):631-634. [7] Polnok A, Verhoef JC, Borchard G,et al.In vitro evaluation of intestinal absorption of desmopressin using drug-delivery systems based on superporous hydrogels[J].Int J Pharm,2004,269(2):303-310. [8] Carreno-Gomez B,Duncan R. Evaluation of the biological properties of soluble chitosan and chitosan mocrospheres[J].Int J Pharm,1997,148(2):231-240. [9] 陈 芳,李 娟. 聚合物胶束载药制备方法研究进展[J]. 亚太传统医药,2014,10(8):48-49. [10] Wagner D, Spahn-Langguth H, Hanafy A, et al. Intestinal drug efflux: formulation and food effects [J]. Adv Drug Deliv Rev, 2001, 50 (Suppl 1): S13-31. [11] 贺云霞,孙 进,程 刚. 多药耐药性P-糖蛋白在药物肠道吸收中的作用[J]. 沈阳药科大学学报,2004,21(5):389-393. -
点击查看大图
计量
- 文章访问数: 2988
- HTML全文浏览量: 398
- PDF下载量: 940
- 被引次数: 0
下载:
