Liposomes in Anti-tumour Drug Carriers

Introduction

Chemotherapy with anti-tumor agents is currently one of the most important systemic treatments for cancer. However, direct treatment with drugs lacks specificity and sensitivity and tends to attack normal cells indiscriminately, resulting in side effects. Liposomes, as drug carriers, provide a superior solution for maintaining or enhancing the efficacy of chemotherapy while reducing the severity of reactions and side effects.

Classification

When the surface of the liposome is modified, the properties of the liposome can be changed to control the release of the internal drug, to achieve better targeting effect and drug efficacy. Current liposome release triggers include heat, light, pH, temperature, ultrasound, enzymes, magnetism and et al., which have been widely used in anti-tumor drug carrier research.

• Conventional liposomes

As a drug delivery system, traditional liposomes can change the pharmacokinetic properties and tissue distribution of tumor drugs, enhance the target aggregation concentration of drugs, and enhance drug efficacy. However, traditional liposomes still have shortcomings such as unsatisfactory targeting distribution characteristics and poor stability, which limit their application in tumor chemotherapy.

• pH-responsive liposomes

pH-sensitive liposomes are destroyed in the acidic environment of the tumor, thereby tending to release antineoplastic drugs to the tumor site. In pH-sensitive liposomes, an important factor that increases sensitivity is the disulfide cross-linking between the precursor molecules.

• Temperature-responsive liposomes

Temperature-sensitive liposomes are lipid microspheres that can carry drugs and release drugs efficiently under high-temperature conditions, which is characterized by a main melting phase transition. At the phase transition temperature, the phospholipid in the liposome transitions from a colloidal state to a liquid crystal state, the encapsulated drug release rate increases, and a higher drug concentration is formed at the target site, which has a strong killing effect on the surrounding tumor cells. However, the drug release is slow when it deviates from the phase transition temperature.

Fig. 1. Liposomal modification for targeted drug delivery (Vinitha R, 2022)

• Magnetic-stimuli responsive liposomes

Magnetic liposomes can be obtained by combining magnetic nanoparticles on the surface of liposomes. When an external magnetic field gradient from a magnetic source is applied, the magnetic nanoparticles on the surface are attracted to the magnetic force. Due to the action of the magnetic force, heat is generated, thus ensuring the release of the drug. The generated heat can also cause a phase transition of the lipid bilayer, resulting in a controlled, triggered release of the drug. They have important implications in the fields of imaging and targeted drug delivery, which also paves the way for the synergistic treatment of tumors with chemotherapy and hyperthermia.

• Photosensitive responsive liposomes

Photosensitive liposomes require light-mediated activation to release drugs and use laser irradiation to activate liposomes to release drugs to kill tumor cells. It is often used in synergistic photodynamic therapy and chemotherapy and immune enhancement therapy for hypoxic tumors.

• Ultrasound responsive liposomes

Due to their favorable physical properties, cost-effectiveness, and non-invasive nature of ultrasound, they are widely used for diagnostic or therapeutic purposes in cancer treatment. When the liposomes are subjected to ultrasound, the vibrations induced induce the nanoparticles to break up the lipid membrane, allowing the drug molecules to be easily released from the lipid membrane.

• Targeted liposomes

Coating the surface of liposomes with hydrophilic polymers such as polyethylene glycol is an easy way to achieve targeted drug delivery, which tends to minimize subsequent uptake by the reticuloendothelial system and therefore Circulation time is longer for passive accumulation in cancer tissue.

In addition, various active substances can be coupled to the surface of liposomes to make liposomes have specific targeting properties. Among them, the specific interaction between receptors and ligands can be used to target ligand-labeled liposomes to organs, tissues or cells containing ligand-specific receptors, and the binding of receptors and ligands can promote lipid Internalized into cells. Monoclonal antibodies can also be coupled with liposomes to construct immunoliposomes (or affinity liposomes), and the liposomes can be targeted to specific cells and organs using antigen-antibody-specific binding reactions.

Advantages

• Increase water solubility, protect blood soluble drugs and improve pharmacokinetic and pharmacological properties of drugs.
• Tissue- or cell-specific drug delivery to limit drug accumulation in other non-target organs such as kidney, liver, spleen and improve efficacy.
• Provides a combination of imaging and therapeutic agents to monitor therapeutic efficacy in real time.
• Protect the loaded drug from degradation and prevent adverse exposure of the drug in the environment to slow the release rate of the drug.
• Specific lipid species could reduce drug leakage.

References

1. Ponce AM; et al. Hyperthermia mediated liposomal drug delivery. Int J Hyperthermia. 2006 May; 22(3): 205-13.
2. Vinitha R; et al. Liposomes - A promising strategy for drug delivery in anticancer applications. Journal of Drug Delivery Science and Technology. 2022 October, 76: 103739.