Amyloid-liposome composites as hybrid platforms for doxorubicin delivery.

The feasibility of engineering the sophisticated hybrid drug delivery platforms through the integration of phospholipid vesicles within a matrix of amyloid suspensions has been evaluated. Utilizing the equilibrium dialysis methodology and spectrofluorometric technique, the quantitative analysis of doxorubicin (DOX) encapsulation capacity of diverse phospholipid assemblies, amyloid suspensions, and their corresponding composite systems has been performed. Our findings revealed that the incorporation of negatively charged cardiolipin (CL) into phosphatidylcholine (PC) lipid vesicles significantly enhances DOX encapsulation and retention, while the addition of amyloid fibrils to charged liposomes has minimal impact on the drug binding. The neutral PC liposomes modified with insulin and lysozyme fibrillar suspensions exhibited improved doxorubicin encapsulation and retention compared to unmodified liposomes, thereby displaying a potential for reduced toxicity and prolonged drug action in vivo. Notably, amyloid fibrils alone were found to demonstrate the lower degree of DOX encapsulation and retention as compared to liposomes. Fluorimetric analysis suggests that the presence of insulin and lysozyme fibrils alters the microenvironment of DOX towards a more hydrophobic which is consistent with deeper bilayer penetration. Cumulative data from release kinetics and retention studies along with fluorescence measurements suggest that PC liposome-insulin fibril composites represent the most promising DOX nanocarriers, combining enhanced drug encapsulation, structural stability, and optimal drug location within the bilayer. The results obtained provide valuable insights into the design of protein-lipid nanomaterials for enhanced drug delivery, offering promising avenues for the development of more effective and targeted therapeutic strategies.