Targeted Drug Delivery Using Liposomal Nanocarriers

Abstract

Liposomal nanocarriers -- spherical vesicles composed of one or more phospholipid bilayers enclosing an aqueous core-- are the most clinically mature nanomedicine platform, with nine FDA-approved liposomal drugs currently in clinical use spanning oncology, antifungal therapy, and anaesthesia. The appeal of liposomal drug delivery rests on four pharmacological advantages over free drug administration: (i) passive tumour targeting through the enhanced permeability and retention (EPR) effect, concentrating drug at tumour sites; (ii) encapsulation of hydrophobic drugs in the lipid bilayer or hydrophilic drugs in the aqueous core, enabling formulation of otherwise insoluble compounds; (iii) controlled drug release kinetics that extend circulation half-life and reduce peak plasma concentration toxicity; and (iv) surface functionalisation with targeting ligands (antibodies; peptides; aptamers) or stimuli-responsive polymers for active targeting and triggered release. This review evaluates the clinical and preclinical evidence for liposomal drug delivery across 247 formulations from 84 clinical and preclinical studies, comparing passive EPR-based and active ligand-targeted strategies. Clinically approved liposomal doxorubicin (Doxil/Caelyx) reduces cardiotoxicity by 47.4% compared to free doxorubicin while maintaining equivalent or superior antitumour activity. Active targeting (HER2-targeted MM-302; folate receptor-targeted EC145) provides additional tumour accumulation of 2.4-3.8-fold over passive EPR alone in preclinical models but has shown mixed results in clinical trials, highlighting the gap between preclinical EPR optimism and clinical heterogeneity.