Liposome: A Novel Drug Delivery System

Introduction to Liposome

Liposome was initially identified and described as swollen phospholipid systems, called Banghasomes, by British hematologist Alec D. Bangham, in 1961 at the Babraham Institute, University of Cambridge. Later, the structural description of liposomes was revealed as small systems constituting one or more closed phospholipid bilayers. The liposomal vesicles are considered as either nanoparticles or microparticles due to their wide range of particle sizes, from 20 nm to several µm, and their ability to encapsulate substances of different polarity and type. Further, owing to their flexible physicochemical and biophysical characteristics, which allow easy manipulation to address various delivery requirements, liposomes present as an attractive delivery system.

Formation of Liposomes

The liposomal vesicle is derived from hydration of phospholipids, which are amphiphilic molecules having a hydrophilic head group and two hydrophobic acyl-tails. The phospholipid molecules self-assemble into a bilayered structure in an aqueous environment, where the polar groups of phospholipid align within the bilayer to create a water-attracting surface, while their lipophilic chains face each other to provide a water-free zone. The phospholipid bilayers continuously surround the dispersing aqueous media and create a vesicular system in response to mechanical shaking or heating. The hydrophobic portion contains two fatty acid chains with 10-24 carbon atoms, while the hydrophilic part primarily consists of phosphoric acid linked to a water-soluble molecule. Furthermore, a wide variety of drugs and macromolecules, including DNA, proteins, and imaging agents, can be encapsulated in liposomal vesicles due to their unique ability to entrap both lipophilic and hydrophilic substances.

Liposomal Drug Delivery Platforms

Primarily, there are four types of liposomal drug delivery platforms, which include:

• Conventional Liposomes: These liposomes consist of a lipid bilayer composed of cationic, anionic, or neutral phospholipids and cholesterol, surrounding an aqueous core. The lipid bilayers and the aqueous space can incorporate the hydrophobic or hydrophilic compounds.
• PEGylated Liposomes: These liposomes consist of modified behavior and characteristics a that are incorporated by the addition of a hydrophilic polymer coating, such as polyethylene glycol (PEG), to the liposome surface in order to provide steric stabilization.
• Ligand-targeted Liposomes: These liposomes can be employed for site- specific targeting by attaching ligands (including antibodies, peptides, and carbohydrates) to their surface or to the terminal end of the attached PEG chains.
• Theranostic Liposomes: This represents a single system consisting of a nanoparticle, a targeting element, an imaging and a therapeutic component.

Therapeutic Applications of Liposomes in Drug Delivery

In comparison to existing formulations, liposomes offer greater therapeutic efficacy and safety. The various therapeutic applications of liposomes in drug delivery have been highlighted in the figure.

Methods for Liposome Preparation

Liposomes can be prepared using various methods that involve combining lipids with aqueous media, and in some way modifying the liposomes characteristics, such as size, lamellarity and encapsulation efficiency. Further, the most fundamental stages involved in liposome formulation include dissolution of lipids in organic solvents, drying of the resultant solution, hydration of dried lipid (using various aqueous media), isolation of liposomal vesicles and performing quality control assays. The figure presents various methods used for liposome preparation.

Liposome Analysis and Characterization Methods

Following production, liposome formulations are subjected to evaluation process in which the physicochemical characteristics of liposomes that influence their biological performance and shelf stability, are assessed. The figure highlights several parameters considered during liposome characterization.

Pharmaceutical and Industrial Applications of Liposomes

Liposomes are frequently used for the delivery of drugs, genes, vaccines, and diagnostic products. Other applications of liposomes include the encapsulation of food and cosmetic materials, along with routine chemical analysis. Currently, there are several liposomal formulations clinically approved for the treatment of various diseases, including cancer, fungal and viral infections, and many are currently in advanced stages of clinical studies. The figure highlights various applications of liposomes in pharmaceutical and other industrial segments.

Challenges in Liposome Development and Manufacturing

Although recent studies have shown encouraging advances in the liposome related therapeutics, there are several challenges that severely hinder development and manufacturing of liposomes. The most common drawback of liposomes is associated with their poor stability under shelf and in vivo conditions. This is mainly caused by the possibility of lipid oxidation and hydrolysis, leakage and loss of hydrophilic cargos, along with particles fission and fusion. Currently, some of these issues can be circumvented by experimenting with formulation adjuvants, such as antioxidants, or post-preparation processing, such as freeze-thawing and freeze-drying. Another major challenge is the manufacturing of liposomes on large-scale since it is a multi-step and multi-test process and therefore, the innovation in this domain is essential.

Future Perspectives

Owing to various advantages offered by liposomes, advanced liposome technologies are being developed to fully substructure the therapeutic applications of liposomes and extensive research is being conducted to develop methods for liposomal formulation with high level of purity and sensitivity. Despite several advancements, there are various challenges in development of liposomes, for which stakeholders are leveraging the expertise of various contract service providers offering development and manufacturing services. These service providers are actively upgrading their capabilities and infrastructure to accommodate the demand for these vesicles. Driven by the growing research efforts, development of advanced methods for preparation and characterization of liposomes, and efforts of various stakeholders, this segment of industry is likely to witness noteworthy growth in the foreseen future.

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