Liposomes have excellent biocompatibility and rarely cause adverse reactions. Its amphiphilic structure can encapsulate water-soluble and hydrophobic active pharmaceutical ingredients (API), making it an ideal drug delivery tool. A similar product, lipid nanoparticles, has attracted much attention for its ability to effectively deliver therapeutic payloads, including vaccine components such as DNA and mRNA. It delivers payload with high precision and achieves highly specific binding.

Feb 20th,2024 1115 견해

What are liposomes?
Liposomes are one of the most extensively studied drug carriers due to their biocompatibility and biodegradability. Liposomes have a unique vesicle structure composed of a lipid bilayer. These bilayers are mainly composed of amphoteric phospholipids with an aqueous space inside. Therefore, we can encapsulate any water-soluble/hydrophilic component in the aqueous cavity of liposomes or lipophilic/lipophilic components in a lipid bilayer.
Phospholipids and sphingomyelin are components of membranes

In a paper published by Professor A.D. Bangham of the United Kingdom, he demonstrated for the first time the method of preparing liposomes containing solutes. Since then, liposomes have been developed as delivery vehicles for drugs and pharmaceuticals. At present, many liposome preparations have been used in clinical applications to deliver drugs with anti-cancer, anti-inflammatory, antibacterial, antifungal, anesthetic and other effects, as well as gene therapy.
What are the characteristics of liposomes?
1. Targeting: Liposomes can selectively enter certain tissues or organs of the human body, such as the liver and spleen. The concentration of liposomal drugs in the liver is 200 to 700 times that of ordinary drugs, so it is also called a "drug missile";

2. Sustained release: Since the drug is wrapped in liposomes and the diffusion rate is reduced, liposome preparations can delay the excretion and metabolism of the kidneys and prolong the action time;

3. Reduce drug toxicity: The liposome phospholipid bimolecular membrane is similar to the mammalian cell membrane, which can reduce the body's immune response and is less likely to cause allergic and other immune reactions. For example, liposomal amphotericin B reduces cardiotoxicity;

4. Improve stability: Drugs stored for a long time are easy to deteriorate, but under the protection of the liposome molecular layer, the possibility of oxidative degradation of the drug is greatly reduced, thus extending the storage time of the drug;

5. Multiple administration routes: Liposomes can be made into various preparations, not only for intravenous administration, but also for subcutaneous, intramuscular injection and mucosal administration, and can also be made into liniments, oral liquids, etc.;

6. Controllable drug distribution: Because liposomes have targeting properties, their surface properties can be changed during the preparation process, thereby changing their targeting properties and controlling the distribution of drugs in tissues and organs in the body.
Liposome Design for Drug Delivery

Beyond the many advantages of liposomes as drug carriers, what are their limitations?
1. Preparation technology threshold: The preparation technology of liposomes requires certain professional knowledge and skills, which may pose certain challenges to commercial production. The complexity and cost of the preparation process may be prohibitive for some companies.

2. Encapsulation rate problem: For some water-soluble drugs, the encapsulation rate of liposomes may be low, which means that the content of the drug in the liposome is limited and it is easy to leak out of the liposome, reducing the drug's efficiency.

3. Stability challenges: Liposomes may face stability issues during storage and transportation. The composition of liposomes may change, leading to degradation or ineffectiveness of the drug. The recent lyophilization method may be an effective method to extend the storage life of liposomes, but this still requires further research and improvement
lipid nanoparticles
In the 1990s, people began to realize the need to develop new nanoparticles that did not rely solely on traditional lipid components such as phospholipids. Lipid nanoparticles represent a relatively new colloidal drug delivery system. The main advantages of lipid nanoparticles compared to traditional encapsulated lipid colloidal systems (liposomes) are their dynamic stability and rigid morphology.
Liposomes vs Lipid Nanoparticles
Liposomes and lipid nanoparticles are indeed similar in design, but they differ slightly in composition and functionality. Both are lipid nanoformulations and are excellent drug delivery tools that deliver targeted ingredients within a protective outer layer of lipids. However, in applications, lipid nanoparticles can take many different forms.
The left picture shows liposomes, the right picture shows lipid nanoparticles

Lipid nanoparticles have a similar structure to liposomes and are particularly suitable for encapsulating various nucleic acids (RNA and DNA). Therefore, they are one of the most commonly used nonviral gene delivery systems. In the recent study "Overview of mRNA Lipid Nanoparticle COVID-19 Vaccine", researchers used lipid nanoparticles as mRNA carriers, fully demonstrating the importance of lipid nanoparticles in this field.

Traditional liposomes typically consist of one or more lipid bilayers surrounding an aqueous cavity and are therefore called lipid vesicles or liposomes. However, not all lipid nanoparticles have a continuous bilayer structure. Some lipid nanoparticles adopt a micelle-like structure that encapsulates drug molecules in a non-aqueous core. This structural change makes lipid nanoparticles flexible in different applications and can meet different drug delivery needs. Therefore, lipid nanoparticles have broad application prospects in research and medical fields as non-viral gene delivery systems and drug carriers.
Pegylation of lipid nanoparticles and liposome drug delivery structures
The main components of lipid nanoparticles usually include cationic lipids and other lipid components. These ingredients include:
Cationic lipids: These lipid molecules have a positive charge and are often used to interact with negatively charged nucleic acids, such as RNA or DNA, to form stable complexes.

Neutral phospholipids: Usually belonging to the phosphatidylcholine (PC) class, these neutral phospholipid molecules play an important role in building the bilayer of lipid nanoparticles. They help maintain the structure and stability of lipid nanoparticles.

Sterols, such as cholesterol: These components play a role in enhancing membrane fluidity and stability in the construction of lipid nanoparticles. Cholesterol is often added to improve the membrane properties of lipid nanoparticles.

PEGylated phospholipids: This refers to polyethylene glycol (PEG) polymers covalently attached to the phospholipid head groups. PEGylation helps improve the stability of lipid nanoparticles, slowing their clearance by the immune system and prolonging their circulation time.

The combination of these lipid components can be tailored to the specific application and desired properties to achieve efficient delivery and release of drugs or nucleic acids. The design and optimization of lipid nanoparticles has broad applications in areas such as drug delivery and gene therapy.

PEGylated phospholipids play an important role in lipid-based drug carriers, mainly in the following aspects:
Providing a "stealth effect": PEGylation allows drug nanoparticles to reduce the risk of being recognized and cleared by the immune system as they circulate in the body. This "invisible effect" helps extend the circulation time of drugs in the blood and improves the efficiency of drug delivery. The polyethylene glycol layer reduces the adsorption of plasma proteins to the liposome surface, thus protecting the nanoparticles from attack by the immune system.

Improved stability: PEGylated phospholipids help improve the stability of liposome-like nanostructures. This is especially important for liposomes of smaller size, as they may fuse with each other or reduce surface tension in vivo, leading to problems with drug loss or uneven mixing. PEGylation can increase the stability of nanoparticles and ensure the durability of drug encapsulation.

Clinical application: Polyethylene glycol liposomes and lipid nanoparticles have been widely used in clinical applications, especially in the field of cancer treatment. They have excellent delivery effects as drug carriers and have become an important component of many cancer therapies.

Application in COVID-19 vaccines: Recent COVID-19 vaccines, such as those from Moderna and Pfizer, use polyethylene glycol liposomes as auxiliary materials to encapsulate messenger RNA (mRNA). These liposome technologies have good vaccine delivery properties and help ensure effective delivery and stability of vaccines.

Overall, PEGylated liposomes have played an important role in drug delivery and vaccine development, improving drug efficacy and stability and providing critical support for the successful application of many therapeutic methods.

References
[1] Gao W, Hu C-MJ, Fang RH, Zhang L. Liposome-like Nanostructures for Drug Delivery. Journal of materials chemistry B, Materials for biology and medicine. 2013;1(48):10.1039/C3TB21238F. doi:10.1039/C3TB21238F. [NCBI]

[2] Kraft JC, Freeling JP, Wang Z, Ho RJY. Emerging Research and Clinical Development Trends of Liposome and Lipid Nanoparticle Drug Delivery Systems. Journal of pharmaceutical sciences. 2014;103(1):29-52. doi:10.1002/jps.23773. [NCBI]

[3] Theresa M. Allen, Pieter R. Cullis. Liposomal drug delivery systems: From concept to clinical applications. Advanced Drug Delivery Reviews. 2013 Jan;65(1):36–48