Manca Maria-Letizia, Mourtas Spyridon, Dracopoulos Vassileios, Fadda Anna Maria, Antimisiaris Sophia G
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
Colloids Surf B Biointerfaces. 2008 Apr 1;62(2):220-31. doi: 10.1016/j.colsurfb.2007.10.005. Epub 2007 Oct 11.
Various types of rifampicin (RIF)-loaded microparticles were compared for their stability during nebulization. Poly(lactide-co-glycolide) (PLGA), chitosan (CHT) and PLGA/CHT microparticles (MPs) were prepared by emulsion or precipitation techniques. MPs ability to be nebulized (NE%) as well as stability during freeze-drying or/and nebulization (NEED%), were evaluated after RIF extraction from MPs and determination by light spectroscopy. MP mean diameters and zeta-potential values were measured by dynamic light scattering, morphology was assessed by SEM, cytotoxicity by MTT method and mucoadhesive properties by mucin association. In all cases, freeze-drying prior to nebulization did not affect EE%, NE or NEED%. In CHT, MPs RIF encapsulation efficiency (EE%) decreased with increasing CHT concentration (viscosity) and CHT-MP NEED% was higher when the polymer was crosslinked by glutaraldehyde. PLGA MPs, exhibited both higher RIF EE% and also higher nebulization ability and NEED%, compared to CHT ones, but also higher cytotoxicity. However, when the two polymers were combined in the PLGA/CHT MPs, EE%, NE% and NEED% increased with increasing MP CHT-content. PLGA/CHT MPs with 0.50% or 0.75% CHT exhibited highest EE% for RIF and also best nebulization ability and stability, compared to all other MP formulations studied. Additionally they had good mucoadhesive properties and comparably low cytotoxicity.
比较了各种负载利福平（RIF）的微粒在雾化过程中的稳定性。通过乳液或沉淀技术制备了聚（丙交酯-共-乙交酯）（PLGA）、壳聚糖（CHT）和PLGA/CHT微粒（MPs）。从MPs中提取RIF并通过光谱法测定后，评估了MPs的雾化能力（NE%）以及冻干或/和雾化过程中的稳定性（NEED%）。通过动态光散射测量MPs的平均直径和zeta电位值，通过扫描电子显微镜评估形态，通过MTT法评估细胞毒性，通过与粘蛋白结合评估粘膜粘附特性。在所有情况下，雾化前的冻干均不影响包封率（EE%）、NE或NEED%。在CHT中，MPs的RIF包封率（EE%）随着CHT浓度（粘度）的增加而降低，当聚合物用戊二醛交联时，CHT-MP的NEED%更高。与CHT微粒相比，PLGA微粒表现出更高的RIF EE%、更高的雾化能力和NEED%，但细胞毒性也更高。然而，当两种聚合物在PLGA/CHT MPs中组合时，EE%、NE%和NEED%随着MP CHT含量的增加而增加。与所有其他研究的MP制剂相比，含有0.50%或0.75% CHT的PLGA/CHT MPs对RIF表现出最高的EE%，以及最佳的雾化能力和稳定性。此外，它们具有良好的粘膜粘附特性和相对较低的细胞毒性。
