N,N,N-三甲基壳聚糖作为吸入给药的渗透促进剂：与模型肺表面活性剂的相互作用
N,N,N-Trimethyl chitosan as a permeation enhancer for inhalation drug delivery: interaction with a model pulmonary surfactant
AI总结：
本文研究了N,N,N-三甲基壳聚糖（TMC）作为吸入渗透促进剂与模拟肺表面活性剂Curosurf的相互作用，发现TMC会引发Curosurf脂质囊泡在尺寸和层状结构上的深刻重组，并指出肺表面活性剂对阳离子电荷的中和可能抑制TMC的渗透促进能力。
摘要：
N,N,N-三甲基壳聚糖（TMC）是一种生物相容且可生物降解的壳聚糖衍生物，目前被用作渗透促进剂以增加肺部药物向血液的转运。本文探讨了TMC对模拟肺表面活性剂Curosurf的影响，Curosurf是一种低粘度脂质制剂，用于患有急性呼吸窘迫综合征的早产儿。Curosurf与TMC表现出强烈的相互作用，导致在静电荷化学计量比下形成聚集体。在纳米尺度上，Curosurf的脂质囊泡在大小和层状结构方面发生了深刻重组。初始微米级囊泡（平均尺寸4.8微米）让位于约300纳米大小的单层囊泡泡沫状网络。在此类条件下，肺表面活性剂对阳离子电荷的中和可能抑制TMC的渗透促进能力，特别是在低TMC含量下发现静电荷络合时。随后应评估肺表面活性剂中和的TMC的渗透特性，以确定其作为肺泡区域吸入渗透促进剂的适用性。
英文摘要：
N,N,N-Trimethyl chitosan (TMC), a biocompatible and biodegradable derivative of chitosan, is currently used as a permeation enhancer to increase the translocation of drugs to the bloodstream in the lungs. This article discusses the effect of TMC on a mimetic pulmonary surfactant, Curosurf, a low-viscosity lipid formulation administered to preterm infants with acute respiratory distress syndrome. Curosurf exhibits a strong interaction with TMC, resulting in the formation of aggregates at electrostatic charge stoichiometry. At nanoscale, Curosurf undergoes a profound reorganization of its lipid vesicles in terms of size and lamellarity. The initial micron-sized vesicles (average size 4.8 microns) give way to a froth-like network of unilamellar vesicles about 300 nm in size. Under such conditions, neutralization of the cationic charges by pulmonary surfactant may inhibit TMC permeation enhancer capacity, especially as electrostatic charge complexation is found at low TMC content. The permeation properties of pulmonary surfactant-neutralized TMC should then be evaluated for its applicability as a permeation enhancer for inhalation in the alveolar region.
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