Alginate nanoparticles as a novel drug delivery system for Alzheimer's disease treatment

Abstract

Nanotechnology has emerged as a promising approach for developing innovative treatments for neurodegenerative diseases such as AD. The limited effectiveness of current therapies is largely attributed to the poor ability of drugs to cross the BBB. Recent advancements in biocompatible NPs have led to the creation of drug delivery systems (DDS) that offer minimal toxicity, superior BBB penetration, and improved transport of drugs with low water solubility. In this work, the application of ALG NPs for the treatment of AD is considered, with a focus on antioxidant therapy. Using the emulsion method, NPs with optimized properties for brain drug delivery were successfully synthesized. Key formulation parameters were adjusted to achieve a highly biocompatible and stable system, with particle sizes averaging around 12 nm (close to the ideal size for effective BBB penetration). A key aspect of the research involved optimizing surface charge, as positively charged NPs exhibit higher uptake across the BBB. However, attempts to achieve this through surfactant or cationic polymer coatings presented challenges, including undesirable increases in particle size and polydispersity. Ferulic acid (FA), a phytochemical with potent antioxidant activity, was selected as a model drug. Its successful encapsulation and loading into the NPs were confirmed using HPLC, demonstrating the system’s effectiveness in drug incorporation. To enhance therapeutic specificity, the NPs were functionalized with mitochondrial-targeting ligands. Of the ligands tested, (3-carboxypropyl)-triphenylphosphonium bromide (TPP) showed the most promising results. In contrast, the synthetic dendrons “G1” and “G2” faced significant solubility limitations and resulted in low functionalization yields. The most efficient strategy for ligand attachment proved to be the pre-functionalization of ALG before NPs synthesis. Although further optimization and comprehensive biological evaluation are necessary, the findings of this study establish a solid foundation for future research in the development of targeted nanotherapeutics for neurodegenerative diseases like AD.