The conformational change and associated aggregation of β amyloid (Aβ) with or without metals is the main cause of Alzheimers' disease (AD). In order to further understand the effects of Aβ and its associated metals on the aggregation mechanism, the influence of Aβ conformation on the metal affinity and aggregation was investigated using circular dichroism (CD) spectroscopy. The Aβ conformation is dependent on pH and trifluoroethanol (TFE). The binding of metals to Aβ was found to be dependent on the Aβ conformation. The aggregation induced by Aβ itself or its associated metals is completely diminished for Aβ in 40% TFE. Only in 5% and 25% TFE can Aβ undergo an α-helix to β-sheet aggregation, which involve a three-state mechanism for the metal-free state, and a two-state transition for the metal-bound state, respectively. The aggregation-inducing activity of metals is in the order, Cu²⁺ > Fe³⁺ ≥ Al³⁺ > Zn²⁺.

The properties of amyloid fibrils, e.g., unique structural characteristics and superior biocompatibility, make them a promising vehicle for drug delivery. Here, carboxymethyl cellulose (CMC) and whey protein isolate amyloid fibril (WPI-AF) were used to synthesize amyloid-based hybrid membranes as vehicles for the delivery of cationic and hydrophobic drugs (e.g., methylene blue (MB) and riboflavin (RF)). The CMC/WPI-AF membranes were synthesized via chemical crosslinking coupled with phase inversion. The zeta potential and scanning electron microscopy results revealed a negative charge and a pleated surface microstructure with a high content of WPI-AF. FTIR analysis showed that the CMC and WPI-AF were cross-linked via glutaraldehyde and the interacting forces between membrane and MB or RF was found to be electrostatic interaction and hydrogen bonding, respectively. Next, the in vitro drug release from membranes was monitored using UV-vis spectrophotometry. Additionally, two empirical models were used to analyze the drug release data and relevant rate constant and parameters were determined accordingly. Moreover, our results indicated that in vitro drug release rates depended on the drug–matrix interactions and transport mechanism, which could be controlled by altering the WPI-AF content in membrane. This research provides an excellent example of utilizing two-dimensional amyloid-based materials for drug delivery.