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。