姜黄素醇质体的体外释放及在体胃肠吸收研究
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摘要
目的:探究姜黄素醇质体(curcunmin ethosomes,CMET)的体外释放特征及在体胃肠吸收情况。方法:文中分为姜黄素(curcumine,CM)、姜黄素脂质体(curcumine liposome,CMLP)和CMET 3组,采用动态透析法考察体外释放特征;建立大鼠在体单向灌流模型,分别给予CM、CMLP和CMET,考察胃和各肠段中CM的吸收情况。结果:CMET在释放介质(p H 1.2 HCl,p H6.8 PBS)中的累积释放率分别为(87.77±0.20)%和(84.72±0.53)%,分别是CM的2.25倍和2.26倍,释放曲线均符合Weibull模型。CMET在大鼠十二指肠、空肠、回肠、结肠等各肠段的吸收速率常数值分别是11.28、5.24、6.12、5.93×10-2 L/min,分别为CM的1.9、1.1、1.6、2.6倍,CMET在四肠段的有效渗透率值分别是9.15、4.21、5.11、6.41×10-3 cm/s,分别为CM的2.4、1.3、1.8、3.2倍。统计分析结果提示,CMET在胃、十二指肠、回肠、结肠的吸收速率常数与CM差异有统计学意义(P分别为0.006、0.007、0.001、0.004)。CMET在十二指肠、空肠、回肠、结肠的有效渗透率与CM差异有统计学意义(P分别为0.000、0.028、0.000、0.005)。结论:CMET能改善药物的体外释放行为,促进小肠对CM的吸收。
Objective:To investigate the in vitro release characteristics and in vivo gastrointestinal absorption of curcumin ethosomes(CMET). Methods:Curcumin(CM)group,curcumin liposome(CMLP)group,and CMET group were established in this study. The dynamic dialysis method was used to evaluate in vitro release characteristics. A rat model of in vivo single-pass perfusion was established and CM,CMLP,and CMET were administered,respectively,to investigate the absorption of CM in the stomach and intestinal segments. Results:The cumulative release rates of CMET in the release media(p H 1.2 HCl,p H 6.8 PBS)were(87.77±0.20)% and(84.72±0.53)%,respectively,which were 2.25 and 2.26 times those of CM,respectively,and the release curves were consistent with the Weibull model. The absorption rate constants(Ka)of CMET in the duodenum,the jejunum,the ileum,and the colon were 11.28×10-2,5.24×10-2,6.12×10-2,and 5.93×10-2 L/min,respectively,which were 1.9,1.1,1.6,and 2.6 times those of CM;the effective permeability(Peff)values of CMET in these four intestinal segments were 9.15×10-3,4.21×10-3,5.11×10-3,and 6.41×10-3 cm/s,respectively,which were 2.4,1.3,1.8,and 3.2 times those of CM. The statistical analysis showed that there were significant differences between CMET and CM in Ka in the duodenum,the jejunum,the ileum,and the colon(P=0.006,0.007,0.001,and 0.004,respectively)and Peff in these four intestinal segments(P=0.000,0.028,0.000,and 0.005,respectively). Conclusion:CMET can improve the in vitro release behavior of CM and promote the absorption of CM in the small intestine.
Objective:To investigate the in vitro release characteristics and in vivo gastrointestinal absorption of curcumin ethosomes(CMET). Methods:Curcumin(CM)group,curcumin liposome(CMLP)group,and CMET group were established in this study. The dynamic dialysis method was used to evaluate in vitro release characteristics. A rat model of in vivo single-pass perfusion was established and CM,CMLP,and CMET were administered,respectively,to investigate the absorption of CM in the stomach and intestinal segments. Results:The cumulative release rates of CMET in the release media(p H 1.2 HCl,p H 6.8 PBS)were(87.77±0.20)% and(84.72±0.53)%,respectively,which were 2.25 and 2.26 times those of CM,respectively,and the release curves were consistent with the Weibull model. The absorption rate constants(Ka)of CMET in the duodenum,the jejunum,the ileum,and the colon were 11.28×10-2,5.24×10-2,6.12×10-2,and 5.93×10-2 L/min,respectively,which were 1.9,1.1,1.6,and 2.6 times those of CM;the effective permeability(Peff)values of CMET in these four intestinal segments were 9.15×10-3,4.21×10-3,5.11×10-3,and 6.41×10-3 cm/s,respectively,which were 2.4,1.3,1.8,and 3.2 times those of CM. The statistical analysis showed that there were significant differences between CMET and CM in Ka in the duodenum,the jejunum,the ileum,and the colon(P=0.006,0.007,0.001,and 0.004,respectively)and Peff in these four intestinal segments(P=0.000,0.028,0.000,and 0.005,respectively). Conclusion:CMET can improve the in vitro release behavior of CM and promote the absorption of CM in the small intestine.
引文
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[16]吕凤娇,许小平.阿霉素纳米粒体外释放模型的拟合研究[J].计算机与应用化学,2010,27(7):915-918.
[17]王煜斐,张亚洲,刘丽萍.姜黄素纳米制剂的改善治疗应用研究进展[J].中药材,2018,49(4):1009-1012.
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[19]王云山,张洪,张晓春.姜黄素醇质体体外透皮及其稳定性研究[J].中国药师,2014,17(10):1640-1642.
[20]Yong TZ,Li NS,Zhong HW,et al.Evaluation of skin viability effect on ethosome and liposome mediated psoralen delivery via cell uptake[J].J Pharm Sci,2014,103(10):3120-3126.
[2]张英,李冬梅,邢颖.姜黄素的药理作用与载体研究进展[J].中国药房,2015,26(13):1850-1853.
[3]Karewicz A,Bielska D,Gzyl-Malcher B,et al.Interaction of curcumin with lipid monolayersand liposomal bilayers[J].Colloids and Surf B Biointerfaces,2011,88(1):231-239.
[4]吴莺,陈瑞家,吴丽贤,等.姜黄素衍生物C085对K562细胞的作用及机制研究[J].中国药理学通报,2015,31(6):870-875.
[5]Kundu P,Mohanty C,Sahoo SK.Antiglioma activity of curcuminloaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy[J].Acta Biomater,2012,8(7):2670-2687.
[6]项松涛,赵明,史现勋,等.RDP多肽修饰的姜黄素隐形脂质体脑靶向作用的研究[J].中国药理学通报,2015,31(8):1136-1141.
[7]李琦,金剑,许颖.姜黄素的药理作用及其临床应用进展[J].现代中西医结合杂志,2012,21(12):1366-1368.
[8]毕文杰,穆小静.姜黄素新型靶向制剂研究进展[J].中国药学杂志,2015,50(4):323-329.
[9]Abdel Messih HA,Ishak RA,Geneidi AS.Nanoethosomes for transdermal delivery of tropisetron HCl:multi-factorial predictive modeling,characterization,and ex vivo skin permeation[J].Drug Dev Ind Pharm,2017,43(6):958-971.
[10]Mbah CC,Builders PF,Attama AA.Nanovesicular carriers as alternative drug delivery systems:ethosomes in focus[J].Expert Opin Drug Deliv,2014,11(1):45-59.
[11]Tan QY,Wang N,Yang H,et al.Characterization,stabilization and activity of uricase loaded in lipid vesicles[J].Int J Pharm,2010,384(1-2):165-172.
[12]晏声蕾,胡江波,王薛,等.吴茱萸碱水包油型复合纳米乳的体外释放和在体吸收研究[J].重庆医科大学学报,2018,43(1):135-138.
[13]陈学梁,赵静,赵华,等.溴吡斯的明纳米乳的体外释放及体内动力学研究[J].重庆医科大学学报,2018,43(1):139-141.
[14]罗建春,何丹,杨梅,等.去甲氧基姜黄素羟丙基-β-环糊精在体肠吸收特征[J].第二军医大学学报,2016,37(2):247-250.
[15]孙全,杨林,陈学梁,等.溴吡斯的明纳米乳体外释放行为评价[J].中国医院药学杂志,2015,35(2):132-135.
[16]吕凤娇,许小平.阿霉素纳米粒体外释放模型的拟合研究[J].计算机与应用化学,2010,27(7):915-918.
[17]王煜斐,张亚洲,刘丽萍.姜黄素纳米制剂的改善治疗应用研究进展[J].中药材,2018,49(4):1009-1012.
[18]董伟,刘辉.姜黄素抗肿瘤新剂型研究进展[J].第二军医大学学报,2015,36(7):771-775.
[19]王云山,张洪,张晓春.姜黄素醇质体体外透皮及其稳定性研究[J].中国药师,2014,17(10):1640-1642.
[20]Yong TZ,Li NS,Zhong HW,et al.Evaluation of skin viability effect on ethosome and liposome mediated psoralen delivery via cell uptake[J].J Pharm Sci,2014,103(10):3120-3126.