Zaru Marco, Mourtas Spyridon, Klepetsanis Pavlos, Fadda Anna Maria, Antimisiaris Sophia G
Department of Pharmacy, University of Patras, Rio, Greece.
Eur J Pharm Biopharm. 2007 Nov;67(3):655-66. doi: 10.1016/j.ejpb.2007.04.005. Epub 2007 Apr 18.
Preparation of drug-loaded freeze-dried (FD) liposomes, designed for delivery to lungs after rehydration/nebulization was investigated. Rifampicin (RIF) incorporating multilamelar (MLV) and dried rehydrated vesicles (DRV); composed of phosphatidylcholine (PC), dipalmitoyloglycero-PC (DPPC) or distearoyloglycero-PC (DSPC), containing or not Cholesterol (Chol), were prepared. Vesicles were characterized for encapsulation efficiency (EE%), size distribution, zeta-potential, stability during freeze drying (FD) and nebulization (nebulization efficiency (NE%) and retention of RIF after nebulization (NER%)). Mucoadhesion and toxicity in A549 cells was measured. RIF EE% was not affected by liposome type but lipid composition was important; Synthetic lipid vesicles (DPPC and DSPC) had higher EE% compared to PC. As Chol increased EE% decreased. Freeze drying (FD) had no effect on EE%, however trehalose decreased EE% possibly due to RIF displacement. NER% was highly affected by lipid composition. Results of NE% and NER% for RIF-loaded liposomes show that DSPC/Chol (2:1) is the best composition for RIF delivery in vesicular form to lungs, by nebulization. Mucoadhesion and A549 cell toxicity studies were in line with this conclusion, however if mucoadhesion is required, improvement may be needed.
研究了用于复水/雾化后肺部给药的载药冻干脂质体的制备。制备了包含多层脂质体（MLV）和干燥复水囊泡（DRV）的利福平（RIF），其由磷脂酰胆碱（PC）、二棕榈酰甘油磷脂酰胆碱（DPPC）或二硬脂酰甘油磷脂酰胆碱（DSPC）组成，含有或不含有胆固醇（Chol）。对囊泡的包封率（EE%）、粒径分布、zeta电位、冻干（FD）和雾化过程中的稳定性（雾化效率（NE%）和雾化后利福平的保留率（NER%））进行了表征。测定了其在A549细胞中的黏膜黏附性和毒性。RIF的EE%不受脂质体类型的影响，但脂质组成很重要；与PC相比，合成脂质囊泡（DPPC和DSPC）具有更高的EE%。随着Chol含量增加，EE%降低。冻干（FD）对EE%没有影响，然而海藻糖可能由于RIF的置换而降低了EE%。NER%受脂质组成的影响很大。载RIF脂质体的NE%和NER%结果表明，DSPC/Chol（2:1）是通过雾化将RIF以囊泡形式递送至肺部的最佳组成。黏膜黏附性和A549细胞毒性研究与该结论一致，然而如果需要黏膜黏附性，则可能需要改进。
