不同助县剂对环孢素A羟丙甲纤维素酞酸酯纳米粒大鼠口服后体内相对生物利用度的影响

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HP55)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-HP55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,2 g/L卡波普,5 g/L黄原胶,8、5、3 g/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550 、362、105、30和15 mPa*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.

Influence of suspending agents on relative bioavailability of cyclosporine A-loaded HPMCP nanoparticles for oral administration to rats

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 mPaxs, 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.