Li Cao-Cao, Zhang Zhen-Hai, Zhang Yin-Long, Lü Hui-Xia, Zhou Jian-Ping
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2013 Jan;48(1):131-7.
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-R8 and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.
为研究硬脂酸-八聚精氨酸(SA-R8)修饰的载紫杉醇固体脂质纳米粒(SA-R8-PTX-SLN)的大鼠肠道吸收情况,并与市售紫杉醇制剂(泰素)及载紫杉醇固体脂质纳米粒(PTX-SLN)作比较,采用大鼠肠道单向灌流技术考察SA-R8-PTX-SLN的原位肠道吸收。在不同肠段、不同药物浓度及存在P-糖蛋白抑制剂(维拉帕米)的情况下考察各制剂的吸收情况。结果显示,紫杉醇在各肠段均可吸收,三种制剂在十二指肠均呈现最大吸收。各肠段三种制剂的累积吸收量表现为SA-R8-PTX-SLN>PTX-SLN>泰素(P<0.05)。在考察的药物浓度范围内,SA-R8-PTX-SLN在十二指肠呈现线性吸收方式。制剂中加入P-糖蛋白抑制剂(维拉帕米)后,泰素和PTX-SLN的累积吸收量显著提高(P<0.05),但SA-R8-PTX-SLN与未加维拉帕米的制剂相比吸收无显著差异(P>0.05)。SA-R8和SLN可能均能有效改善紫杉醇在肠道的口服吸收。