History, Introduction, and Physicochemical Properties and Characterization Parameters of Liposomes Publisher



Morad H ; Rostamnezhad M ; Rezaei S ; Negarandeh R ; Wang F
Source: Fundamentals and Therapeutic Applications of Liposomes Published:2025

Abstract

Liposomes, discovered in 1965 by Alec D. Bangham, have developed from model membrane systems to clinically approved drug delivery nanocarriers, with significant steps including PEGylation, remote loading methods, and the 1990s approvals of Doxil and AmBisome. This chapter explains their historical evolution across three eras genesis (1968–1975), middle age (1975–1985), and modern era (post-1985), emphasizing on applications in cancer therapy, infectious diseases, gene delivery, and vaccination. Liposomes are phospholipid-based vesicles that self-assemble into unilamellar (SUV, LUV) or multilamellar (MLV, MVV) structures, entrapping hydrophilic agents in hydrophilic cores and hydrophobic agents through bilayers. The physicochemical characteristics like size (20 nm–2.5 μm), size distribution, zeta potential (±20–30 mV for stability), membrane fluidity, and permeability are modified by lipid composition, cholesterol concentration, and preparation techniques (e.g., lipid film hydration, ethanol injection, reverse-phase evaporation) to optimize entrapment efficiency, controlled release, and passive targeting through the enhanced permeability and retention (EPR) phenomenon. Characterization studies, including dynamic light scattering (DLS), electron microscopy (TEM, SEM, cryo-TEM), zeta potential analyzes, fluorescence anisotropy, and differential scanning calorimetry (DSC), lead to critical insights into morphology, stability, drug loading (passive vs. active), and biological interactions. Challenges like immune clearance, scale-up, and long-term stability are provided via surface modifications and advanced manufacturing. The chapter reviews approved formulations and predict future prospectives in stimuli-responsive, ligand-targeted, and hybrid liposomal systems for precision medicine. © 2026 Elsevier Ltd. All rights reserved.