Engineering chitosan-functionalized liposomes for targeted drug delivery and biomedical applications

Chitosan (CS) is a naturally derived cationic polysaccharide that has attracted sustained interest in drug delivery due to its favorable biocompatibility, biodegradability, and chemical versatility. Liposomes are well-established lipid-based nanocarriers capable of encapsulating both hydrophilic and hydrophobic therapeutics; however, their clinical performance is often compromised by limited physicochemical stability, premature drug leakage, rapid clearance, and insufficient interaction with biological barriers. Surface functionalization of liposomes with CS has emerged as an effective hybridization strategy that integrates the structural advantages of lipid bilayers with the mucoadhesive, stabilizing, and tunable surface properties of CS. This review systematically summarizes the design rationale, fabrication methods, and physicochemical characteristics of CS-functionalized liposomes, with particular emphasis on how CS coating influences colloidal stability, drug loading efficiency, release kinetics, and interactions with cells and tissues. The preparation strategies for both CS nanoparticles and liposomes are discussed to provide a foundation for understanding the formation and optimization of CS-liposome hybrid systems. In addition, the impact of CS functionalization on different administration routes, including intravenous, ocular, nasal, transdermal, and oral delivery, is critically examined. The biomedical applications of CS-functionalized liposomes are comprehensively reviewed, covering cancer therapy, antimicrobial treatment, antioxidant and anti-inflammatory interventions, phototherapy, wound healing, and the management of fibrotic and inflammatory lesions. Across these applications, CS coating is shown to enhance liposomal stability, bioadhesion, cellular uptake, and controlled or stimuli-responsive drug release, while also providing a versatile platform for further functionalization with targeting ligands or responsive moieties. Overall, CS-functionalized liposomes represent a flexible and multifunctional drug delivery platform that addresses key limitations of conventional liposomes and CS nanoparticles when used independently. By combining lipid-based encapsulation with polymer-mediated stabilization and targeting, these hybrid systems hold considerable promise for the development of next-generation nanomedicines and translational biomedical applications.