【摘要】 目的 :研究不同助悬剂对环孢素A (CyA)羟丙甲纤维素酞酸酯 (HPMCP ,型号HP5 5 )纳米粒 (NP)大鼠体内相对生物利用度的影响。方法 :以黄原胶、羟丙甲纤维素和卡波普为助悬剂来稳定CyA HP5 5纳米粒。大鼠灌胃服用加入不同助悬剂的纳米粒 ,用HPLC法测定全血中的药物浓度。以CyA商品制剂新山地明 (Neoral)为参比 ,计算助悬纳米粒的相对生物利用度 ,并用 3P97计算药物动力学参数。结果 :几种助悬纳米粒的血药浓度 -时间数据均以二室模型和权重 1/C2 拟合最佳。以Neoral为参比 ,2g/L卡波普 ,5g/L黄原胶 ,8、5、3g/L羟丙甲纤维素助悬纳米粒的相对生物利用度分别为 70 .2 % ,84 .3% ,90 .0 % ,94 .5 %和 97.7% ,这五种助悬纳米粒对应的黏度分别为 5 5 0、36 2、10 5、30和 15mPa·s。结论 :随着助悬剂黏度的增大 ,纳米粒的相对生物利用度下降。在选择助悬剂稳定纳米粒时 ,应综合考虑助悬纳米粒的物理稳定性与生物利用度两方面的因素。更多还原

【Abstract】 Objective:To study the influence of suspending agents on the relative bioavailability of Cyclosporine A-loaded HPMCP(HP55) nanoparticles for oral administration. Methods: Suspending agents such as Vanzan,HPMC,Carbopol were added into cyclosporine A-loaded HP55 nanoparticles. The suspended nanoparticle formulations and Neoral were administered orally in a dosage of 15 mg/kg to rats. The CyA concentrations in the blood sample were determined by HPLC. Pharmacokinetic parameters were calculated by 3P97. Results: The concentration-time data of these preparations were best fit by two compartment model with a weight of 1/C 2. Compared with the reference Neoral microemulsion, the relative bioavailability of 2 g/L Carbopol,5 g/L Vanzan,8,5,3 g/L HPMC suspended nanoparticles were 70.2%, 84.3%,90.0%,94.5% and 97.7%, respectively. Their viscosity values were 550, 362, 105, 30 and 15 mPa·s, respectively. Conclusion: With the increase in viscosity, the relative bioavailability of nanoparticle formulations decreased. So, it is important to select the appropriate viscosity of suspending agents in the formulation design.更多还原