Surface modified liposomes for targeted drug delivery applications: A Review

Abstract

Liposomes are self-assembled phospholipid bilayer vesicles that function as versatile drug delivery systems by accommodating both hydrophilic and hydrophobic therapeutic agents. This review examines the classification, preparation, characterization, and applications of liposomes, with particular emphasis on surface modification strategies that enhance targeting efficiency and therapeutic efficacy. Liposomes are categorized by size, lamellarity, lipid composition, and surface characteristics, with small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs), and multilamellar vesicles (MLVs) constituting the principal classes. Surface modifications, notably poly (ethylene glycol) (PEG) conjugation (PEGylation) and ligand functionalization, improve colloidal stability, prolong systemic circulation, and enable site-specific delivery. Passive targeting exploits the enhanced permeability and retention (EPR) effect, whereas active targeting employs antibodies, peptides, and aptamers to engage receptors overexpressed on target cells. Stimuli-responsive systems, including pH-sensitive, thermosensitive, magneto responsive, and near-infrared (NIR)-responsive liposomes, permit spatiotemporally controlled drug release. Nevertheless, PEGylation is limited by the accelerated blood clearance (ABC) phenomenon and anti-PEG immune responses, which have stimulated the development of alternative stealth coatings such as zwitterionic polymers and poly (2-oxazoline)s (POx). Recent advances in lipid–polymer hybrid systems have further expanded the functional repertoire of liposomal carriers, yet challenges of scalability, batch-to-batch reproducibility, immunogenicity, and regulatory approval persist. This review underscores the capacity of surface-modified liposomes to overcome key limitations of conventional drug delivery and to improve therapeutic outcomes, particularly in oncology, and outlines the characterization and quality-by-design (QbD) frameworks required for their clinical translation.