Role of Amyloid Nanofibrils in Drug Incorporation and Release from Wrinkled Supraparticles

Nanoparticle aggregates, termed supraparticles (SPs), exhibit a range of promising properties. In the pharmaceutical field, changing the type or ratios of the building blocks that constitute the SP may alter the SP morphology but also significantly improve its function as a drug delivery carrier or biomaterial. Our previous work demonstrated that wrinkled SPs can be prepared by incorporating amyloid nanofibrils (ANFs) into the spray-drying precursor. Despite this advancement, the application of wrinkled SPs as pharmaceutical excipients remains underexplored, and the impact of ANFs and drug loading on dissolution profiles is not well understood. In this study, we examine the influence of drug loading on the SP morphology and drug dissolution characteristics from the SPs. The present findings reveal that the model drug, carvedilol (CVD), is incorporated into the spray-dried SPs in an amorphous state. The morphology of CVD-loaded SPs is greatly influenced by the ANF content, leading to observed variations in size and wrinkle fold thickness. The dissolution profiles of CVD from SPs varied considerably based on the SP composition, predominantly exhibiting a burst release mechanism. The presence of ANFs reduced the CVD release rate. Both the loading and release rate of CVD were modulated by the SP composition. These results suggest that ANFs are a viable component for designing drug delivery systems, although they are not sufficient to significantly modulate the burst release phase, indicating the necessity for additional or alternative components to achieve controlled release of drugs.