Liposomes: Bridging the gap from lab to pharmaceuticals

Abstract

Liposomes are versatile and effective drug delivery systems, as highlighted by various medical applications. Their well-defined bilayer structure is suited for the encapsulation of drugs with diverse chemical properties and for a variety of release strategies. Understanding liposome self-assembly and structure is crucial for enhancing drug development and delivery efficiency. Herein, we review the self-assembly process of liposomes and transfer this knowledge to means of production.

The challenges and opportunities of scaling liposomal production are discussed. Key techniques, to characterize the particles, their interface and composition, essential for market approval, are outlined. Views on novel computational methods to deepen the lipid behavior at interfaces and accelerate liposome development are given, including opinions on using artificial intelligence to support liposome production.

Introduction

Liposomal drug delivery is a well-established modality in clinical practice, representing a significant milestone in nanomedicine. Notably, the approval of Caelyx/Doxil® in the late 90s marked a pivotal achievement, introducing a liposomal doxorubicin formulation for the treatment of ovarian, breast cancer, and Kaposi’s sarcoma [1]. Subsequent to this success, a cascade of small-molecule chemotherapy drugs reached the market as liposomal formulations (Figure 1), enhancing pharmacokinetic properties and mitigating off-target adverse effects [2, 3].

During the same timeframe, other liposomal products emerged for indications other than cancer, including virosomal vaccines like Epaxal® and Inflexal V®. A decade later, liposomal depot systems for pain management, such as DepoDur® and Exparel®, obtained marketing authorization [2]. Recently approved liposomes have expanded to include therapeutic proteins as vaccines, as seen with Mosquirix™ and Shingrix®, reflecting the evolving applications of liposomes in nanomedicine [2, 3, 4∗].

Despite growing interest, liposomal drug development faces unresolved challenges [4]. Parenteral liposomal formulations have encountered limitations in encapsulating certain macromolecules or high therapeutic doses of hydrophobic compounds, due to the limited capacity within the bilayer. The choice and composition of lipids play a crucial role in addressing these challenges, influencing the overall efficacy of liposomes as drug delivery systems. Despite their potential, liposomes exhibit further drawbacks, including scalability issues, high production costs, the risk of drug molecule outflow and fusion during storage and within the body, susceptibility to oxidation, and hydrolysis reactions [5, 6, 7, 8].

The development of liposome drugs also still lacks comprehensive regulatory and standardization guidelines, complicating quality control. The European Medicines Agency (EMA) has released a reflection paper in 2013 on the development of liposomal products with reference to an innovator liposomal product [9]. While there is no guidance document for innovator products from the EMA yet, the reflection paper outlines quality characteristics such as lipid composition, stability, morphology, and size, among others [9]. Later, in 2018, the Food and Drug Administration (FDA) identified several CQAs that need addressing, including lipid species identification, nanoparticle characterization (morphology, structure, particle size distribution, and surface charge), and more [4,10]. Despite the growing interest in nanomedicines, addressing these gaps is crucial to ensuring the safety, efficacy, and regulatory compliance of liposomal formulations.

This review highlights unresolved challenges in parenteral liposomal formulations, paving the way for subsequent discussions on liposome structure and composition, production and downstream processing, and characterization tools. Addressing these challenges is essential for advancing the field of liposomal nanomedicine and fostering regulatory frameworks that ensure quality and safety in drug development.

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Remo Eugster, Paola Luciani, Liposomes: Bridging the gap from lab to pharmaceuticals, Current Opinion in Colloid & Interface Science, Volume 75, 2025, 101875, ISSN 1359-0294, https://doi.org/10.1016/j.cocis.2024.101875.

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