重组人干扰素α-2b脂质体的制备及其家兔体内药动学研究

Preparation of liposomes containing recombinant human interferon α-2b and study on the pharmacokinetics in the rabbits

目的以溶液剂为参比,考察家兔肌肉注射重组人干扰素α-2b脂质体的药动学变化,为研究重组人干扰素α-2b脂质体的长效制剂提供参考。方法以逆向蒸发法制备重组人干扰素α-2b脂质体,以家兔为模型动物,分别单剂量一次注射重组人干扰素α-2b脂质体和参比溶液剂,不同时间采集血液,分离血浆,经处理后,应用双抗体夹心酶联免疫吸附法(ELISA)测定重组人干扰素α-2b的血浆药物浓度。结果家兔分别肌肉注射同剂量的重组人干扰素α-2b脂质体及溶液剂,与溶液剂相比,重组人干扰素α-2b脂质体延缓了药物的吸收,达峰时间延长,体内平均滞留时间(MRT)分别为4.86 h和6.00 h,脂质体组体内滞留时间较溶液剂组延长,脂质组AUC为溶液剂组的1.4倍,体内生物利用度显著提高。结论脂质体作为重组人干扰素α-2b的载体,能够显著延长重组人干扰素α-2b家兔体内平均滞留时间,提高生物利用度,具有潜在应用的价值。

Objective To study the pharmacokinetics in rabbits after i. m. injection of recombinant human interferon α-2 b（ rh IFN α-2 b） liposome as compared with solution of rh IFN α-2 b Methods A reverse-evaporation method was used to prepare the liposome formulations with higher encapsulation of rh IFN-α-2 b. The pharmacokinetic experiment was done by intramuscular administration of rh IFN-α-2 b liposomes and solution in rabbits and then the samples of blood were gathered at indicated time. The double antibody sandwich enzyme-linked immunsorbent assays method（ ELISA） was used to determine the level of IFN α-2 b in plasma. Results Compared with the solution of rh IFN α-2 b,mean residence time（ MRT） value of rh IFN α-2 b liposomes（ 4. 86 h） was greater than that of solution（ 6. 00 h）. The Tmaxobtained from rh IFN α-2 b liposomes was prolonged as compared with solution of rh IFN α-2 b. The AUC0-24 of rh IFN-α2 b in plasma obtained from rh IFN-α2 b liposomes was 1. 4 times greater than that obtained from solution-rh IFN-α2 b. Conclusion Compared with the solution of rh IFN α-2 b,rh IFN α-2 b liposome can significantly prolong the MRT of rh IFN α-2 b and increase the relative bioavailability in rabbits,indicating that liposomes might be a promising delivery carrier for rh IFN α-2 b.