Establishing design principles for spray dried nanofibrillar supraparticles towards modular pulmonary drug delivery systems

建立用于模块化肺部药​​物输送系统的喷雾干燥纳米纤维超颗粒的设计原则

• 批准号: 21K20495
• 负责人: Kamarainen Tero
• 金额: $ 2万
• 依托单位: Osaka Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-08-30 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K20495/
• 关键词: Supraparticles; Amyloid nanofibrils; Spray drying; Silica nanoparticles; Phytoglycogen; Silver nanowires; Crumpling; Tannic acid; Beta-lactoglobulin; Amyloid nanofibril; Drug delivery system; Supraparticle; Nanofibril; Nanoparticle

Amyloid nanofibrils (ANFs) were synthesized (few μm length, ~10 nm width) from whey protein (beta-lactoglobulin, βLG) and their influence on the morphology of spray-dried supraparticles (SPs) was analyzed quantitatively with scanning electron microscopy (SEM). Silica nanoparticles (SNPs; 10, 50, 100 nm diameter) or soft polysaccharide nanoparticles (phytoglycogen; ~50 nm diameter) and silver nanowires (SNWs) were used as the SP nanoparticle fraction. We found that ANFs enhance the morphological crumpling of SPs compared to βLG control, indicating faster onset of structural arrest during the SP consolidation due to the high aspect-ratio of ANFs. The crumpling transition could be further modulated by ultrasonic breakup of ANFs to shorter lengths (lower aspect-ratio). Crumpled SP shapes occurred at higher ANF content with increasing SNP size, while soft nanoparticles impeded crumpling at low ANF content. Hollow SP shapes were not observed likely due to crumpling being favored by large drying stresses and plasticity afforded by ANFs. Results on SNW-containing SPs are too preliminary to draw conclusions.Structural integrity of ANFs after spray drying remains unclear. Field-emission SEM could not discern ANFs on SP surfaces. Transmission electron microscopy of never-dried SPs were inconclusive on the presence of ANFs, while water-dispersed SPs displayed short ANF segments.These results have direct relevance to SP particle interactions, aerodynamic/drug release properties and clearance by illuminating the control of SP shape/surface area, and indirectly, their cohesiveness.

从乳清蛋白（β-乳球蛋白，βLG）合成淀粉样蛋白纳米纤维（ANF）（长度几微米，宽度约 10 纳米），并用扫描电子显微镜（SEM）定量分析它们对喷雾干燥超颗粒（SP）形态的影响二氧化硅纳米颗粒（SNP；直径 10、50、100 nm）或软多糖纳米颗粒（植物糖原；~50 nm）和银纳米线（SNW）用作 SP 纳米颗粒部分，我们发现与 βLG 对照相比，ANF 直径增强了 SP 的形态皱缩，表明由于 SP 固结过程中结构停滞的开始更快。高纵横比的 ANF 可以通过超声破碎进一步调节 ANF 的长度（较低的纵横比）。随着 SNP 尺寸的增加，ANF 含量增加，而在 ANF 含量较低时，软纳米粒子阻碍了褶皱，这可能是由于较大的干燥应力和 ANF 提供的可塑性有利于褶皱的产生。得出结论。喷雾干燥后 ANF 的结构完整性仍不清楚。场发射 SEM 无法识别 SP 表面上的 ANF。从未干燥的 SP 对于 ANF 的存在并无定论，而水分散的 SP 显示出短的 ANF 片段。这些结果通过阐明 SP 形状/表面积的控制，与 SP 颗粒相互作用、空气动力学/药物释放特性和清除率直接相关，以及间接地，他们的凝聚力。