Zhao Lingyun, Feng Si-Shen, Go Mei Lin
Department of Chemical and Environmental Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore, 119260.
J Pharm Sci. 2004 Jan;93(1):86-98. doi: 10.1002/jps.10523.
Molecular interactions between paclitaxel and dipalmitoylphosphatidyl choline (DPPC) were investigated by Langmuir film balance and differential scanning calorimetry (DSC). Both the lipid monolayer at the air-water interface and that in the lipid bilayer vesicles (liposomes) were employed as model cell membranes. Thermodynamic and kinetic analyses of the DPPC/pacltaxel monolayer system and the paclitaxel penetration into the DPPC monolayer showed that DPPC and paclitaxel can form a nonideal miscible system in the lipid monolayer over a wide range of the DPPC/paclitaxel molar ratios. Paclitaxel exerts an area-condensing effect on the DPPC monolayer at small molecular areas and an area-expanding effect at large molecular areas on the pi-A behavior of the DPPC monolayer, which can be explained by the intermolecular forces and geometric accommodation between paclitaxel and DPPC. Based on a calculation of the excess free energy of the mixed monolayer system, the most stable state of the system occurs at the monolayer composition of 5% paclitaxel. Penetration kinetics showed that the paclitaxel penetration into the DPPC monolayer increases with increasing the drug concentration in the subphase, but there is a limit of approximately 500 ng/mL. Any further increase in paclitaxel concentration had no additional significant effects on the drug penetration. Differential scanning calorimetry showed that paclitaxel caused broadening of the main phase transition. There was no significant change in the peak melting temperature of the DPPC bilayers, which demonstrated that paclitaxel was localized in the outer hydrophobic cooperative zone of the bilayer.
通过朗缪尔膜天平及差示扫描量热法（DSC）研究了紫杉醇与二棕榈酰磷脂酰胆碱（DPPC）之间的分子相互作用。空气 - 水界面的脂质单分子层以及脂质双层囊泡（脂质体）中的脂质单分子层均被用作模型细胞膜。对DPPC/紫杉醇单分子层系统以及紫杉醇渗透进入DPPC单分子层的热力学和动力学分析表明，在较宽的DPPC/紫杉醇摩尔比范围内，DPPC与紫杉醇可在脂质单分子层中形成非理想互溶体系。在小分子面积时，紫杉醇对DPPC单分子层有面积凝聚作用，而在大分子面积时对DPPC单分子层的π - A行为有面积扩张作用，这可以通过紫杉醇与DPPC之间的分子间作用力和几何适配来解释。基于对混合单分子层系统过剩自由能的计算，该系统最稳定的状态出现在紫杉醇单分子层组成为5%时。渗透动力学表明，紫杉醇渗透进入DPPC单分子层的程度随亚相中药物浓度的增加而增加，但存在约500 ng/mL的极限值。紫杉醇浓度的任何进一步增加对药物渗透没有额外的显著影响。差示扫描量热法表明，紫杉醇导致主相变变宽。DPPC双层膜的峰值熔化温度没有显著变化，这表明紫杉醇定位于双层膜的外部疏水协同区。
