目的 通过改变柔性脂质体的磷脂组成实现普萘洛尔透皮吸收性能的最大化。 方法 采用二棕榈酰磷脂酰胆碱(DPPC)与大豆磷脂(SPC)为材料,制备了复合磷脂柔性脂质体,采用硫酸铵梯度法载入普萘洛尔。比较了不同磷脂组成普萘洛尔柔性脂质体的药剂学性质与经皮给药后的药物动力学性质。 结果 复合磷脂组成为6∶4时变形性最高。普萘洛尔复合磷脂(DPPC-SPC=6∶4)与大豆磷脂柔性脂质体的包封率分别为(78.97±2.94)%和(68.67±0.58)% (n=3)。释放度实验表明12 h后普萘洛尔复合磷脂与大豆磷脂柔性脂质体的累积释放度为(23.23±0.90)% 和(39.84±0.51)%(n=3)。经皮给药后,普萘洛尔复合磷脂柔性脂质体的生物利用度显著提高,是大豆磷脂柔性脂质体的14.73倍。 结论 应用复合磷脂组成能够显著提高普萘洛尔柔性脂质体的稳定性和透皮吸收效果。

To enhance the percutaneous absorption of propranolol by modifying the lipid composition of elastic liposomes. METHODS Elastic liposomes composed of both 1,2-dipalmitoyl-sn-glycero-3-phosphacholine(DPPC)and soy phosphatidylcholine(SPC)were prepared and propranolol was encapsulated into liposomes by ammonium sulfate gradient loading method. Then the pharmaceutical and pharmacokinetic properties of propranolol-loaded elastic liposomes(PEL)with different lipid compositions were compared. RESULTS The highest deformability was obtained with PEL composed of binary mixtures of DPPC and SPC(6∶4, molar ratio). The encapsulation efficiency(EE)values of PEL composed of binary mixtures of DPPC and SPC(6∶4, molar ratio)and SPC alone were 78.97±2.94% and 68.67±0.58%, respectively. And the drug release values were (23.23±0.90)% and (39.84±0.51)%, respectively. Following transdermal administration, the bioavailability of PEL composed of binary mixtures of DPPC and SPC(6∶4, molar ratio)was significantly increased(14.73-fold)compared with that of PEL composed of SPC alone. CONCLUSION The membrane stability and percutaneous absorption of PEL can be significantly improved by the application of binary mixtures of DPPC and SPC.