Zaru Marco, Manca Maria-Letizia, Fadda Anna Maria, Antimisiaris Sophia G
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
Colloids Surf B Biointerfaces. 2009 Jun 1;71(1):88-95. doi: 10.1016/j.colsurfb.2009.01.010. Epub 2009 Jan 20.
The preparation of Chitosan (CHT)-coated liposomes and their applicability as a carrier for delivery of drugs to the lungs by nebulisation was investigated. Empty SUV (small unilamellar) liposomes were initially prepared (with different lipid compositions) and coated with CHT by dropwise addition of CHT solution in the liposome dispersion. CHT-coating efficiency was calculated after separation of coated/non-coated liposomes by centrifugation, and measurement of lipid in each fraction. After establishing the best conditions for CHT-coating (concentration of CHT in the solution), RIF-loaded CHT-coated liposomes, with different lipid compositions (negatively charged and non-charged) were constructed, and their encapsulation efficiency (EE) and nebulisation efficiency (NE%)/stability (NER%) were evaluated. Charged liposomes (containing phosphatidylglycerol [PG]) can be coated with CHT better compared to non-charged ones. The EE of CHT-coated liposomes (that contain PG) is slightly increased while their stability after nebulisation is significantly increased (NER%). Mucoadhesive properties of CHT-coated liposomes were substantially better (compared to non-coated ones) while the toxicity of liposomal RIF towards A549 epithelial cells was lower compared to free drug for all the types of vesicles evaluated, and especially the CHT-coated ones. Thereby, it is concluded that CHT-coated liposomes have advantages (compared to non-coated) when the delivery of drugs to the lungs by nebulisation is considered.
研究了壳聚糖（CHT）包被脂质体的制备及其作为雾化给药肺部载体的适用性。首先制备了空的小单层囊泡（SUV）脂质体（具有不同的脂质组成），并通过向脂质体分散液中逐滴加入CHT溶液对其进行包被。通过离心分离包被/未包被的脂质体并测量各部分中的脂质后，计算CHT包被效率。在确定CHT包被的最佳条件（溶液中CHT的浓度）后，构建了具有不同脂质组成（带负电荷和不带电荷）的负载利福平（RIF）的CHT包被脂质体，并评估了它们的包封率（EE）和雾化效率（NE%）/稳定性（NER%）。与不带电荷的脂质体相比，带电荷的脂质体（含有磷脂酰甘油[PG]）可以更好地被CHT包被。CHT包被的脂质体（含有PG）的EE略有增加，而雾化后的稳定性显著提高（NER%）。与未包被的脂质体相比（与未包被脂质体相比）CHT包被脂质体的粘膜粘附性能明显更好，而对于所有评估的囊泡类型，尤其是CHT包被的囊泡，脂质体RIF对A549上皮细胞的毒性低于游离药物。因此，可以得出结论，当考虑通过雾化将药物递送至肺部时，CHT包被的脂质体（与未包被的相比）具有优势。
