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.

以乳清蛋白（β-乳球蛋白，βLG）为原料，制备了长度为几μm，宽度约为10 nm的淀粉样纳米纤维（ANF），并利用扫描电镜（SEM）定量分析了ANF对喷雾干燥超微粒（SPs）形态的影响。二氧化硅纳米颗粒（SNPs; 10、50、100 nm直径）或软多糖纳米颗粒（植物糖原; ~50 nm直径）和银纳米线（SNW）用作SP纳米颗粒级分。我们发现ANF与βLG对照相比增强了SP的形态学皱曲，表明由于ANF的高纵横比，在SP固结期间结构停滞的发生更快。皱曲过渡可以进一步调制由超声波破碎ANF到更短的长度（较低的纵横比）。随着SNP尺寸的增加，在较高的ANF含量下发生起皱的SP形状，而软纳米颗粒在低ANF含量下阻碍起皱。没有观察到中空SP形状，可能是由于ANF提供的大干燥应力和塑性有利于起皱。对含SNW的SPs的研究结果还太初步，无法得出结论。喷雾干燥后ANF的结构完整性仍不清楚。场发射扫描电镜不能分辨SP表面的ANF。透射电子显微镜的从未干燥的SP是不确定的ANF的存在下，而水分散的SP显示短ANF segments.These结果有直接相关的SP颗粒相互作用，空气动力学/药物释放性能和清除照亮SP形状/表面积的控制，并间接，他们的凝聚力。