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.

合成淀粉样纳米纤维（ANFS）（少数μm长，约为10 nm的宽度）与乳清蛋白（β-乳球蛋白，βLG）合成，并用扫描电子显微镜（SEM）定量地分析了对喷雾干燥的苏普拉皮菌（SP）形态的影响。二氧化硅纳米颗粒（SNP； 10、50、100 nm直径）或软多糖纳米颗粒（植物学原成；直径〜50 nm）和银纳米线（SNWS）（SNWS），我们发现与βLG对照相比，SPS的形态巡航与βLG对照相比，在结构上均置于结构上的较高效果。可以通过对ANF的超声破裂至较短的长度（较低的侧面比例）进一步调节巡航过渡。皱巴巴的SP形状在较高的ANF含量下发生，SNP尺寸增加，而软纳米颗粒以低ANF含量阻碍了巡航。没有观察到空心的SP形状可能是由于ANFS所提供的大干燥应力和可塑性所青睐巡航。含SNW的SP的结果太初步了，无法得出结论。喷雾后ANF的结构完整性尚不清楚。现场发射SEM无法在SP表面上辨别ANF。在ANF的存在下，从未干燥的SP的透射电子显微镜尚无定论，而水分散的SP则显示出短的ANF节段。这些结果与SP颗粒相互作用，空气动力学/药物释放特性以及清除率直接相关，通过照亮SP形状/表面积的控制以及间接的凝聚力。