2022 Fiscal Year Research-status Report
Establishing design principles for spray dried nanofibrillar supraparticles towards modular pulmonary drug delivery systems
| Project/Area Number |
21K20495
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| Research Institution | Osaka Medical and Pharmaceutical University |
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Principal Investigator |
Kamarainen Tero 大阪医科薬科大学, 薬学部, 特任研究員 (20909890)
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| Project Period (FY) |
2021-08-30 – 2024-03-31
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| Keywords | Supraparticles / Amyloid nanofibrils / Spray drying / Silica nanoparticles / Phytoglycogen / Silver nanowires / Crumpling |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
The origin of the incurring funds petitioned to be used during the next fiscal year is in the delay caused by material shipping delays to the beginning of the main experimental part of the project, namely spray drying experiments with amyloid nanofibrils. This prevented recurring chemical and material purchases to be made and delayed reaching outcomes that could be presented at conferences.
Finalization of the project requires, e.g., the synthesis of more amyloid nanofibrils and silver nanowires and the purchase of silica nanoparticles so that spray drying and drug release experiments can be carried out fully. The remaining funds will be used to purchase laboratory materials and chemicals as well as cover costs associated with conferences presentations.
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