阿昔洛韦多囊脂质体的制备及在大鼠体内的药动学

Preparation of acyclovir multivesicular liposome and its pharmacokinetics in rats

目的：制备阿昔洛韦多囊脂质体,并考察其体外释放和在大鼠体内药动学。方法：采用复乳法制备阿昔洛韦多囊脂质体,分别以pH 7.4的磷酸盐缓冲液（PBS）和血浆为释放介质考察其体外释放情况;以阿昔洛韦药物溶液为参比制剂进行大鼠肌内注射的药动学研究。结果：阿昔洛韦多囊脂质体在pH 7.4PBS中72～96 h累计释放80%,血浆中释放稍快。大鼠肌内注射阿昔洛韦多囊脂质体10 mg.kg-1后,与注射同样剂量的药物溶液相比,多囊脂质体的达峰时间显著延长[（0.50±0.20）vs（0.17±0.08）h,P〈0.01],峰浓度显著降低[（2.54±1.20）vs（31.50±3.14）mg·L^-1,P〈0.01],消除时间显著延长[（24.14±4.76）vs（1.50±0.21）h,P〈0.01],48 h药物浓度仍可维持在0.4 mg·L^-1。结论：阿昔洛韦多囊脂质体肌内注射缓释效果明显。

Objective： To prepare muhivesicular liposome （MVL） of acyclovir, a depot delivery system, and to evaluate its cumulative release ratio in vitro and the pharmaeokineties in rats. Methods： Aeyelovir MVLs were prepared using multiple emulsion method. The concentration of acyelovir released from MVL in phosphate buffered solution （PBS, pH 7.4） or in plasma was measured. Pharmaeokinetie properties were evaluated in rats following intramuscular injection of acyclovir MVL or the reference aeyelovir solution. Results： Aeyelovir was continuously released from MVL formulations in PBS （pH 7.4） in vitro, and reached a maximum of 80% within 72 to 96 h. Following intramuscular injection （10 mg·kg^-1） in rats, the Tmax was （0.50 ± 0.20） vs （0. 17 ± 0.08）h （P〈0.01）; C was （2.54 ± 1.20） vs （31.50 ±3. 14）mg·L^-1（P 〈0.01）; t1/2 was （24. 14 ±4.76） vs （1.50 ±0.21）h （P 〈 0. 01 ） for acyclovir MVL and solution, respectively. The absorption was slower and the elimination was more prolonged after acyelovir MVL injection; the effective level of plasma concentration （0.4 mg·L^-1） maintained at 48 h. Conclusion： Acyclovir MVL shows a significant sustained-release property.