Liposomes – Challenges and Opportunities

Medical science is continuously searching for better ways to administer drugs into the body and to maximize the therapeutic effectiveness of the drugs given.

Liposome technologies have become an important part of the drug delivery armory, with several marketed products now available for use and many more formulations being evaluated in clinical trials.

The success of liposome-based therapeutics is often attributed to several core factors including relative ease of synthesis, biocompatibility, the ability to load both hydrophilic and hydrophobic agents, and long circulation property after application of polyethylene glycol (PEG).

The first 4-minute mile (the Roger Banister Effect) - FDA approval

When Roger Bannister first achieved the 4-minute-mile, it broke a psychological barrier that ‘allowed’ runners to dream of the impossible. No longer held back, swarms of runners went under the barrier and continue to do so.

While not necessarily a swarm, it was the approval of Doxil (doxorubicin, Johnson & Johnson) in 1995 that truly marked the acceptance of liposome technology for drug delivery applications. There are now many marketed liposome-based drug products available with many more undergoing clinical trials.

Most of the approved liposome-based products are for the treatment of cancer or infectious diseases, where the use of the liposome delivery system has been shown to improve efficacy and/ or reduce the toxicity of the drug used.

What are Liposomes?

Liposomes are spherical vesicles composed of a phospholipid bilayer shell and an aqueous internal compartment, with particle sizes typically ranging from 30 – 3000 nm. The structural similarity of liposomes with living cells has prompted much research into their use as drug and gene delivery agents.

Challenges and opportunities

Liposomes can act as carriers for both hydrophilic materials (within the core) and hydrophobic materials (within the bilayer), which makes them particularly attractive for drug delivery purposes. They are also biocompatible and biodegradable.

Early complications in the use of conventional liposomes as drug carriers included ‘leakiness’, with contents being lost due the fluidity of the bilayer membrane. The inclusion of stiffening agents, such as cholesterol, in the membrane can alleviate this issue. Furthermore, the chemical and physical stability of liposomes can be problematic, leading to issues with handling and storage. Their short survival time in the body has also been considered a limitation.

Subsequently, much research has been conducted to modify the fundamental liposome structure in order to instill more beneficial properties.

Liposomal drug delivery systems and the opportunities they present

Conventional liposome

Liposomes consist of a lipid bilayer that can be composed of cationic, anionic, or neutral (phospho)lipids and cholesterol, which enclose an aqueous core. Both the lipid bilayer and the aqueous space can incorporate and act as carriers for both hydrophobic or hydrophilic compounds, respectively which makes them attractive for drug delivery.

PEGylated liposome

The attachment of a hydrophilic polyethylene glycol (PEG) chain to the outside of the bilayer has been shown to confer steric stabilization and prolong the biological lifetime of liposomes after administration. Consequently, the preparation of PEGylated liposomes has become a popular approach to extending blood circulatory times and localization in tumors as well as other sites of pathology.

PEGylated liposomes are often referred to as ‘stealth’ liposomes due to their ability to evade phagocyte clearance in the blood.

Ligand-targeted liposome

Liposomes can be used for specific targeting by attaching ligands (e.g., antibodies, peptides and carbohydrates) to their surface or to the terminal end of the attached PEG chains. The ligand can bind to receptors on particular cells (e.g. tumor cells) and taken into the cells by means of receptor-mediated endocytosis.

Theranostic liposome

A single system that consists of a nanoparticle, a targeting element, an imaging component and a therapeutic component. A promising modality of nanomedicine and can achieve diagnosis and image-guided therapy through diagnostic-therapeutic integrated functions.

A meeting of minds. Science at its best.

Advances continue to be made in manipulating the properties of liposomes to maximize their usefulness.

In 2019, the Pfizer Melbourne site opened a state of the art liposomal and nanoparticle facility to facilitate market entry of several pre-commercial products.

If you want to know more about the potential of this technology download our paper: Liposomal and Nanoparticle Technology at Pfizer Melbourne, here.