Applications and Design Strategies of Cellulose-Based Drug Delivery Systems for the Treatment of Neurodegenerative Diseases

초록

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis are characterized by a progressive loss of neurons driven by protein aggregation, neuroinflammation, and oxidative stress. Additionally, the blood-brain barrier (BBB) severely restricts the delivery of most therapeutics to the brain. In this context, cellulose and nanocellulose have emerged as sustainable drug delivery systems (DDSs) owing to their renewable biomass-based origin, excellent biocompatibility and biodegradability, high mechanical strength, and abundant surface hydroxyl groups that enable versatile chemical functionalization. This review summarizes the structural and physicochemical properties of bulk, nanocrystal, nanofibril, and bacterial celluloses that are crucial for designing DDSs that can target the brain. These include a high specific surface area, as well as tunable network formation, surface charge, and hydrophilicity. The review highlights representative preclinical applications in major neurodegenerative diseases, such as cellulose ether-based oral formulations that modulate amyloid-β pathology, mucoadhesive carboxymethyl cellulose nasal nanocrystals for nose-to-brain delivery of dopaminergic agents, trehalose-cellulose systems targeting mutant huntingtin aggregation, and chitosan-nanocellulose hydrogels that support neural tissue repair. Finally, it critically discusses the current relevance and limitations of cellulose-based DDSs compared with liposomal and polymeric nanoparticles and outlines future design strategies involving advanced surface functionalization, hybrid and multilayer architectures, integration with neural tissue engineering, and processes for regulatory standardization to enable clinical translation in neurodegenerative disease therapy. © 2025, Korean Technical Assoc. of the Pulp and Paper Industry. All rights reserved.

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