Liposomes as Trojan Horses: Engineering, Mechanisms and Emerging Functionalities in Drug Delivery and Pharmacological Applications

Lipid-based nanocarriers, particularly liposomes, have played a central role in the development of modern drug delivery systems due to their biocompatibility, structural versatility, and ability to encapsulate both hydrophilic and hydrophobic compounds. Initially conceived as passive delivery vehicles, liposomes have progressively evolved into highly tunable and multifunctional platforms capable of addressing key pharmacological challenges such as biodistribution, targeting specificity, and controlled drug release. Beyond their structural advantages, liposomal systems fundamentally alter the pharmacokinetic behavior and disposition of their payloads, modifying drug–transporter interactions, bypassing efflux mechanisms, and reshaping systemic exposure profiles in ways that classical formulations cannot.Despite these advances, significant barriers still hinder their full clinical translation, including limited stability, insufficient targeting efficiency, and incomplete understanding of their interactions with biological membranes and complex cellular environments. Recent research efforts have begun to address these limitations by integrating physicochemical design principles with advanced functionalization strategies and external stimuli-responsive mechanisms.This Research Topic aims to provide a comprehensive and interdisciplinary overview of the current state-of-the-art in liposomal systems, bridging fundamental aspects of membrane physics with pharmacological applications. In particular, we seek to highlight emerging approaches that transform liposomes into “active” nanoplatforms, capable of remote-controlled drug release, biomimetic behavior, and enhanced interaction with cellular and extracellular environments.By bringing together contributions from physics, chemistry, nanotechnology, and pharmacology, this collection aims to advance the conceptual and practical framework of lipid-based drug delivery systems and to accelerate their translation into clinically relevant solutions. All contributions are expected to connect their findings to a pharmacological context, whether through drug efficacy data, mechanistic pharmacological insights, pharmacokinetic characterization, or therapeutic application.Areas of interest include, but are not limited to:• Physicochemical Design of Lipid Nanocarriers: Studies addressing lipid composition, membrane phase behavior, colloidal stability, and structural characterization, including experimental and computational approaches. Studies should connect physicochemical findings to pharmacological relevance, such as implications for drug encapsulation efficiency, release kinetics, or in vivo performance.• Functionalization and Targeting Strategies: Development of liposomes with surface modifications (e.g., PEGylation, ligands, antibodies) to improve targeting efficiency, pharmacokinetics, and modulation of drug transporter interactions, including strategies to overcome efflux-mediated resistance (e.g., P-glycoprotein, BCRP, MRP1).• Stimuli-Responsive and Remote-Controlled Systems: Liposomal platforms activated by pH, temperature, enzymatic activity, or external fields (e.g., magnetic, optical, or acoustic) for controlled drug release. Contributions should include pharmacological validation of the release mechanism, such as in vitro cytotoxicity, cellular uptake assays, or in vivo efficacy data.• Liposomes as Biomimetic Systems: Use of liposomes as biomimetic platforms to study pharmacologically relevant membrane interactions, including cell uptake mechanisms, membrane fusion dynamics, and drug permeation processes. Studies focused exclusively on membrane biophysics without a connection to drug behavior or therapeutic application fall outside the scope of this collection.• Drug and Gene Delivery Applications: Advances in liposome-based delivery systems for cancer therapy, gene delivery, vaccines, and other biomedical applications, including studies addressing therapeutic efficacy, safety profiling, and tolerability of liposomal formulations.• Mechanistic Insights into Membrane Interactions: Investigations into molecular-level interactions between liposomes and biological systems, including membrane permeabilization, vehicle fusion, and drug transport phenomena, such as passive and facilitated diffusion of released drug and interactions with membrane-bound efflux and uptake transporters.• Translational and Clinical Challenges: Studies addressing scalability, reproducibility, regulatory aspects, and the gap between experimental systems and clinical implementation, including pharmacokinetic characterization and physiologically based pharmacokinetic (PBPK) modelling approaches to support preclinical-to-clinical translation. Topic editors: Vicente Domínguez Arca, Narumon Changsan, Somchai Sawatdee, Nagasamy Venkatesh Dhandapani Source: https://www.frontiersin.org/research-topics/82563/liposomes-as-trojan-horses-engineering-mechanisms-and-emerging-functionalities-in-drug-delivery-and-pharmacological-applications