穿膜肽修饰紫杉醇固体脂质纳米粒的大鼠在体肠吸收研究  

In situ rat intestine absorption of paclitaxel-loaded solid lipid nanoparticles modified with cell-penetrating peptides

作　　者：李草草[1] 张振海[2] 张银龙[1] 吕慧侠[1] 周建平[1] 

机构地区：[1]中国药科大学药剂教研室,江苏南京210009 [2]江苏省中医药研究院,江苏南京210028

出　　处：《药学学报》2013年第1期131-137,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30973649;30901867);教育部博士点基金项目(20090096110002;20110096110005);江苏省高校研究生科研创新计划项目(CX10B-373Z)

摘　　要：考察硬脂酸-八聚精氨酸(stearic acid-octaarginine,SA-R8)修饰的紫杉醇(paclitaxel,PTX)固体脂质纳米粒(solid lipid nanoparticles,SLN)在大鼠肠道的吸收情况。以市售制剂(Taxol)和PTX-SLN为对照,采用单向灌流法,研究不同肠段、不同药物浓度及加入P-糖蛋白抑制剂后SA-R8-PTX-SLN的大鼠肠道吸收动力学。结果表明,3种制剂在全肠段都有吸收,且在十二指肠吸收最好。在各个肠段,3种制剂的净累积吸收量表现为SA-R8-PTX-SLN>PTX-SLN>Taxol(P<0.05)。SA-R8-PTX-SLN在十二指肠的吸收在考察药物浓度范围内呈现线性吸收。加入P-糖蛋白抑制剂后,Taxol和PTX-SLN在十二指肠的净累积吸收量均显著提高(P<0.05),而SA-R8-PTX-SLN的净累积吸收量与未加P-糖蛋白抑制剂相比无显著性差异(P>0.05)。因此,SA-R8和SLN共同作用,可显著促进紫杉醇的口服吸收。To investigate the rat intestinal absorption of stearic acid-octaarginine（SA-R8） modified solid lipid nanoparticles containing paclitaxel（SA-R8-PTX-SLN）,compared with the commercially available preparation of PTX（Taxol） and PTX-loaded solid lipid nanoparticles（PTX-SLN）,the in situ intestinal absorption of SA-R8-PTX-SLN was investigated by means of single-pass rat intestinal perfusion technique.The absorptions of the preparations were investigated at different intestinal segments,different drug concentrations and in the presence of P-glycoprotein inhibitor（verapamil）.The results showed that PTX could be absorbed at each intestinal segment and the three preparations all showed maximum absorptions at the duodenum.The cumulative absorptions of three preparations at each intestinal segment appeared SA-R8-PTX-SLN PTX-SLN Taxol（P 0.05）.SA-R8-PTX-SLN showed a liner absorption manner at the duodenum in the examined drug concentration range.The cumulative absorptions of Taxol and PTX-SLN were significantly promoted after the addition of P-glycoprotein inhibitor（verapamil） into the preparation（P 0.05）,but absorption of SA-R8-PTX-SLN existed no significantly difference compared with the preparation without verapamil（P 0.05）.SA-R8and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.

关 键 词：穿膜肽 紫杉醇 固体脂质纳米粒 肠道吸收 

分 类 号：R943[医药卫生—药剂学]