PDF(Pubmed)
Abstract：
The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf®. We show that BUD facilitates the Curosurf® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf® dispersion is maintained for BUD < 10 wt% of the Curosurf® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant\'s lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide-enriched Curosurf®.
摘要：
使用外源性肺表面活性物质（EPS）作为布地奈德（BUD）载体的临床益处，一种具有广泛抗炎作用的非卤化皮质类固醇，已经建立。使用各种实验技术(差示扫描量热法DSC，小角度和广角X射线散射SAXS/WAXS，小角度中子散射SANS，荧光光谱法，动态光散射DLS，和zeta电位)，我们研究了BUD对临床使用的EPS的热力学和结构的影响，Curosurf®。我们表明，BUD促进了Curosurf®从凝胶到流体状态的相变，导致主相变温度（Tm）和焓（ΔH）降低。对于BUD<10重量%的Curosurf®质量,保持Curosurf®分散体的形态;BUD略微增加了多层囊泡(MLV)中流体层状相的重复距离d,这是由于脂质双层的增厚而产生的。双层增厚(〜0.23nm)源自SANS数据。~2mmol/L的Ca2+的存在维持了MLVs的作用和结构。Curosurf®双层侧压的变化表明，当表面活性剂脂质分子的酰基链之间的嵌入BUD含量超过约6wt％时，其位于疏水区域更深。我们的研究支持使用富含布地奈德的Curosurf®的联合疗法的概念。
