研究課題/領域番号 |
21K20495
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研究種目 |
研究活動スタート支援
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配分区分 | 基金 |
審査区分 |
0401:材料工学、化学工学およびその関連分野
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研究機関 | 大阪医科薬科大学 |
研究代表者 |
Kamarainen Tero 大阪医科薬科大学, 薬学部, 特任研究員 (20909890)
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研究期間 (年度) |
2021-08-30 – 2024-03-31
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研究課題ステータス |
交付 (2022年度)
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配分額 *注記 |
3,120千円 (直接経費: 2,400千円、間接経費: 720千円)
2022年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2021年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
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キーワード | Supraparticles / Amyloid nanofibrils / Spray drying / Silica nanoparticles / Phytoglycogen / Silver nanowires / Crumpling / Tannic acid / Beta-lactoglobulin / Amyloid nanofibril / Drug delivery system / Supraparticle / Nanofibril / Nanoparticle |
研究開始時の研究の概要 |
This project studies the preparation of particle aggregates that contain spherical and rod-like bio-based particles and protein-based fibrils towards drug delivery applications. The influence of particle size, shape and material on aggregate assembly, disassembly and drug release are investigated.
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研究実績の概要 |
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.
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現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
During the preceding fiscal year, the most time-consuming part of the project, namely supraparticle (SP) spray drying and the subsequent quantitative analysis of SPs' scanning electron microscopy images, finally commenced after shipping delays (ca. 6 months) of dialysis membranes, needed for the synthesis of amyloid nanofibrils, were resolved. Initially, polyphenolic particles from principal investigator’s previous work were planned to be used as rigid, rod-like particles to study SP consolidation modularity (non-spherical shape, different surface chemistry), however their purification and size control below 1 μm had proven challenging, therefore in the interest of saving time, silver nanowires were selected as an alternative due to their shape uniformity and facile size control via ultrasonic treatment and the use of polyphenolic particles were no longer pursued. Phytoglycogen, readily available in appropriate size and high purity, was selected as the polysaccharide nanoparticle. Steps to finalize the project in this fiscal year are given in the Plans for the Research Scheme section.
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今後の研究の推進方策 |
Ongoing work addresses the ability of amyloid nanofibrils (ANFs) to modulate supraparticle (SP) morphology containing rigid, rod-like silver nanowires and rigid/soft spherical nanoparticles. Thereafter, aerodynamic properties of select supraparticles will be characterized using a cascade impactor. These results will be the focus of publication #1 currently in preparation. Supraparticle drug dissolution studies are underway, which will assess the influence of ANFs on the SP disintegration kinetics and drug release properties when dispersed in aqueous medium. These results will be disseminated in publication #2 during the second half of this fiscal year.
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