槲皮素巯基化壳聚糖微球的制备、表征及大鼠体内药代动力学
Preparation, characterization and pharmacokinetics of thiolated-chitosan microspheres loading quercetin in rats
-
摘要: 以槲皮素为模型药物，制备巯基化壳聚糖微球。考察微球的巯基含量、载药量、形态、吸水前后的形态及体外释放，评价微球的离体胃肠黏附性及大鼠体内药代动力学。结果表明，微球的巯基含量为(147.0±8.2)μmol/g，载药量为(5.33±0.12)%；扫描电镜结果表明载药微球上存在一定的孔道；显微镜下观察发现，微球在加入水中后体积迅速膨胀，呈圆球状，释放后微球仍较为完整。考察了微球在水、人工胃液、人工肠液等不同介质下的体外释放行为，经溶出曲线相似因子评价，微球在各介质中的释放行为极为相似，符合Higuchi方程Q=0.161t1/2。黏膜黏附实验表明巯基化壳聚糖微球的黏附性明显增强。同剂量灌胃给药后，槲皮素巯基化壳聚糖微球在大鼠体内的生物利用度显著高于混悬剂及壳聚糖微球，有望成为槲皮素很有前景的制剂之一。Abstract: Thiolated-chitosan microspheres(Thio-Cs-Ms)loading quercetin(QT)as model drug were prepared. The thiol group content, drug-loading capability, morphology in SEM and in microscope before and after hydration, release in vitro and pharmacokinetics in rats were evaluated. The thiol group content was(147. 0±8. 2)μmol/g, the drug-loading capability was(5. 33±0. 12)%. There were several pores on the surface of microspheres observed in SEM images. The microspheres expanded to be sphericity immediately after hydrating, and their morphology were intact after release in microscope. The behavior of release in vitro were no significant difference in water, simulated gastric fluid and simulated intestinal fluid evaluated by dissolution curve similarity factor. The release of Thio-Cs-Ms was fit for Higuchi equation Q=0. 161t1/2. Thio-Cs-Ms exhibited enhancing muco-adhesive ability in excised stomach and intestinal experiments. The bioavailability of Thio-Cs-Ms was obviously higher than that of suspension and Cs-Ms loading quercetin after oral administration in rats. Thio-Cs-Ms loading quercetin might to be one of the most promising preparations of quercetin.
-
Keywords:
- quercetin /
- thiol /
- chitosan microspheres /
- pharmacokinetics
-
-
[1] Bischoff SC.Quercetin:potentials in the prevention and therapy of disease[J].Micronutrients,2008,11(6):733-740. [2] Bernkop-Schnürch A,Hornof M,Guggi D.Thiolated chitosans[J].Eur J Pharm Biopharm,2004,57(1):9-17. [3] Makhlof A,Werle M,Tozuka Y,et al.Nanoparticles of glycol chitosan and its thiolated derivative significantly improved the pulmonary delivery of calcitonin[J].Int J Pharm,2010,397(1/2):92-95. [4] Iqbal J,Shahnaz G,Perera G,et al.Thiolated chitosan:development and in vivo evaluation of an oral delivery system for leuprolide[J].Eur J Pharm Biopharm,2012,80(1):95-102. [5] Dubey RR,Parikh RH Two-stage optimization process for formulation of chitosan microspheres[J].AAPS PharmSciTech,2004,5(1):E5. [6] Sakloetsakun D,Hombach JM,Bernkop-Schnürch A.In situ gelling properties of chitosan-thioglycolic acid conjugate in the presence of oxidizing agents[J].Biomaterials,2009,30(31):6 151-6 157. [7] Rahmat D,Sakloetsakun D,Shahnaz G,et al.Design and synthesis of a novel cationic thiolated polymer[J].Int J Pharm,2011,411(1/2):10-17. [8] Akiyama YN,Nagahara T,Kashihara S,et al.In vitro and in vivo evaluation of mucoadhesive microspheres prepared for the gastrointestinal tract using polyglycerol esters of fatty acids and a poly(acrylic acid)derivative[J].Pharm Res,1995,12(3):397-405. [9] Hollman PC,van Trijp JM,Buysman MN,et al.Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man[J].FEBS Lett,1997,418(1/2):152-156. -
期刊类型引用(0)
其他类型引用(1)
计量
- 文章访问数: 1268
- HTML全文浏览量: 0
- PDF下载量: 1832
- 被引次数: 1
下载:
