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基于白蛋白纳米粒的中空性纳米聚集颗粒 (LHNAs) 是一种用于治疗肺部疾病的新型药物递送系统 (DDS),其由于具有良好的空气动力学特性有望成为一种有前途的肺部干粉吸入剂 (DPI).深入理解DDS中的分子作用机制有利于制剂的合理制备.本研究利用计算和实验相结合的方法揭示了布地奈德 (BUD) 与牛血清白蛋白 (BSA) 在分子水平上相互作用的机制.分子动力学模拟结果显示,BUD和BSA有三个结合位点 (P1,P2,P3),作用方式主要为疏水相互作用和氢键.P1–P3处的残基能量分解结果表明BUD与BSA结合位点周围的非极性残基具有重要作用.载药率实验表明制剂中BUD与BSA摩尔比接近3,进一步证实了计算模拟的结果.计算得到的关于BUD与BSA结合位点的细节为设计包载BUD的BSA纳米颗粒提供了指导,并最终成功制备了纳米粒.分子动力学模拟和实验的结合揭示分子间相互作用机制,为今后制备BSA-LHNAs干粉吸入剂提供了坚实的理论基础.“,”Large Hollow nanoparticulate aggregates (LHNAs) based on albumin nanoparticles is a promising technology for developing dry powder inhaler (DPI) with good aerodynamic properties in order to provide a new drug delivery system (DDS) for the treatment of lung disease. Improved understanding of molecular interactions could lead to prepare the DDS rationally. Therefore, this investigation utilized computations and experiments to reveal the mechanisms of budesonide (BUD) interactions with bovine serum albumin (BSA) at the molecular level. The molecular dynamics (MD) simulation revealed that there were three critical stable binding sites of BUD on BSA (P1, P2, P3) mainly by hydrophobic interaction and hydrogen bond. The energy decomposition of each residue to the whole BUD-BSA complex system in P1-P3 showed that nonpolar residues in or around the binding site played an important role in the binding of BUD to BSA. The molar ratio was close to 3 in preparations in drug-loading efficiency experiment, which was confirmed to the simulation results. The details of the binding sites from computation provided a guideline for the design of the BSA nanoparticles carrying BUD, which was prepared successfully at last. Combination of the MD simulation and experiment as well as the mechanism of the molecular interaction provided a solid theoretical basis for the preparation of BSA-LHNAs for DPI in the future.