Liposome and nanoliposome

The liposome is a spherical and closed lipid layer that forms a cavity within itself that is capable of carrying some aqueous solutions and other compounds such as drugs.

What is liposome?

"Liposomes" (Liposome) are two or more layered structures that consist of solid phospholipid sheets. These structures were first introduced in the mid-1960s. These molecules have a hydrophobic tail and a hydrophilic head region. When two individual membranes are brought together, the hydrophobic tails are attracted to each other, while the hydrophilic heads of both membranes face water.

This process forms a spherical double or double layer of phospholipid molecules. This phospholipid sphere can hold and transport aqueous solutions. Solutions can be delivered with liposomes if necessary.

There are two other lipid structures called "micelles" and "lysosome" which should not be confused with liposome. A micelle is a spherical phospholipid structure that, unlike a liposome, consists of a single layer.

Picture 1: The difference between micelle and liposome structure

The lysosome is one of the specialized organelles in cells that separates and stores decomposing enzymes from other parts of the cell. This organelle is very similar to a liposome, but in its phospholipid structure there are proteins that help its function as a cell organelle.

Classification of liposomes

The size of liposomes can be as small as 0.025 to as large as 2.5 µm. For this reason, these particles are included in the scope of nanotechnology. Also, liposomes can be single-walled or multi-walled (from two phospholipid layers). The size of liposomes is a factor that determines the half-life of these structures in the body's circulatory system. In general, liposomes are classified based on their size and phospholipid layers:

Multi Lamellar Vesicles or (MLV): multi-walled liposomes with a size of more than 400 nm

Large Unilamellar Vesicles or (LUV): single-walled liposomes with a size of about 100-400 nm

Small Unilamellar Vesicles (SUV): single-walled liposomes with a size of about 25-100 nm

Figure 2: Classification of liposomes based on size

Liposomes are classified into three different categories based on their nature and composition:

Stealth Liposomes: Due to their surface receptors, these liposomes can avoid being phagocytosed by the cells of the immune system and remain in the body for a longer period of time. These liposomes are used for drugs that require long-term release in the body. The surface receptor used for these liposomes is usually polyethylene glycol (PEG).

Conventional liposomes: They are among the most widely used liposomes. This group has a negative charge due to the amount of phospholipids and cholesterol they have and are used to deliver drugs to different tissues.

Targeted liposomes: Targeted liposomes can specifically deliver drugs to a specific tissue or cell. Antibodies are placed on the surface of these liposomes so that they can identify the cell in question.

Cationic liposomes: This group of liposomes have a positive charge due to having some cations on their surface and are mostly used in gene therapy.

Figure 3: Types of liposomes based on nature and function

How are liposomes formed?

When tissue is destroyed, liposomes are produced naturally. In fact, when the cells of a tissue are damaged, small parts of the cell membrane are separated from them. These phospholipid fragments can bend on themselves and make spherical structures and enclose small packages of any type of solution inside them. These structures are formed because the hydrophilic and hydrophobic interactions between separate lipid fragments It is created from cells and aqueous solutions around them. These interactions make the two ends of the lipid fragments connect to each other and make a spherical structure, whose internal environment is completely separated from its external environment. The production of liposomes with this process can also be done artificially in the laboratory.

Using a sound wave generator, scientists can use sound waves to break the layers of the lipid membrane into liposomes of whatever size they want. Sound waves carry a lot of energy that breaks the lipid bilayer molecules apart and turns them into separate parts. These fragments are then exposed to the same forces that naturally create liposomes, and in this way liposomal spheres are made.

Synthesis methods of liposomes

Due to the many uses of liposomes, these lipid structures are synthesized in different ways. All liposome synthesis methods include 4 main steps:

Lipid drying from organic solvents

Lipid dispersion in aqueous medium

Purification of the resulting liposome

Analysis and review of the final product

Based on the type of compound we want to carry with the liposome, there are two methods of loading:

Active loading: This type of transport is used to load amphiphilic compounds (hydrophilic and hydrophobic) after liposome formation.

Passive loading: Passive loading is performed for hydrophilic and hydrophobic compounds before liposome formation.

Liposome synthesis methods for passive loading include:

Mechanical dispersionE from the waves of Sony kit

Freezing and thawing of liposomes

French cell pressure

Microemulsification

Membrane dissolution

Solvent release

Detergent removal

Picture 4: Sony kit device for producing liposomes

Applications of liposomes

Liposomes have useful properties that have doubled their importance for application in many fields of cell science, medicine and health. In this article, we will examine some of the applications of liposomes in different fields.

Application of liposome in cellular studies

Liposomes are used as a model for the cell membrane and its organelles in cell studies. By placing different proteins in the structure of these two lipid layers, scientists can identify the function of the outer and inner proteins of the cell membrane. Liposomes have played a significant role in advancing "Modern Cell Theory".

By studying the non-living and visible structures of liposomes, researchers were able to predict and identify the cellular methods used to transfer and transport different chemical compounds.

The activities and functions of the endoplasmic reticulum and the Golgi apparatus, in the packaging and processing of cellular products, are directly related to the way liposomes work.

Cells simply add different proteins to the surface of their organelles to direct and control the interaction of different organelles. So that the function of proteins on organelles can be created and studied in liposomes.

The use of liposomes in the manufacture of cosmetic products

In recent years, liposomes have become delivery systems for active ingredients in cosmetic products. Liposomes facilitate the passage of the active ingredient of cosmetic products into the epidermis. Liposomes are not only a tool for transferring cosmetic active ingredients to the inner layers of the skin, but also increase their stability in the skin and increase skin moisture by surface adhesion. Liposomes protect skin cells from external damaging factors such as sunlight, and for this reason, liposome technology is used in many sunscreens. The use of liposomes to transfer effective cosmetic ingredients in various products such as creams, lotions, and shampoos is a revolution in the cosmetic industry.

Picture 6: How liposomes enter and release cosmetic active ingredients into skin cells

Application of liposome in food industry

The use of particles in the nano size range in food industry products is called food nanotechnology. In this technology, nanosystems are used to transfer effective substances and antimicrobial agents to food products. One of these nanosystems are nanoliposomes. In the food industry, nanoliposomes containing antimicrobial or antifungal agents are used in food products to increase shelf life and reduce food spoilage. Also, nanoliposomes are used to encapsulate some flavorings and enzymes with the aim of gradually releasing them in food products.

Application of liposome in therapeutic methods

Liposomes are very important in various medical fields, including pharmaceuticals, especially for delivering toxic and dangerous drugs to specific targets. Liposomes that are used in the human body for drug delivery and other applications must be in nanometer dimensions to enter the body and move in it, that's why the liposomes that transport in the human body are also called "nanoliposome". Medical information in this The field has shown that liposomes can deliver antitumor drugs to tumor cells by increasing drug efficiency and reducing toxicity to the body. Here we mention some of the advantages of using liposomes in medicinal and therapeutic applications:

Liposomes improve the solubility of lipophilic and amphiphilic drugs (with both hydrophilic and hydrophobic ends).

Increasing the stability of the drug occurs when it is placed in the liposome space.

Liposomes are non-toxic, flexible, biocompatible and biodegradable.

Liposomes reduce drug toxicity in the body by encapsulating the drug inside.

Liposomes reduce exposure of sensitive tissues to toxic drugs.

Liposomes reduce the side effects of the drug.

Flexibility to pair with specific receptors to reach the target cells is also a characteristic of liposomes.

Figure 6: Types of drug delivery liposomes; Liposomes have different forms based on the type of drug they carry and the target cell of the drug. Some of them, which have to specifically transfer the drug to a certain cell, have protein receptors of the type of antibody to identify the cell.

Anti-cancer treatments

As mentioned, liposomes can also be used in new drug delivery methods. For example, some cancer drugs that are dangerous to healthy body cells are packaged in liposomes and delivered specifically to cancer cells.

The function of such liposomes has a simple theory. On the surface of liposomes that are used for drug delivery purposes, there are embedded proteins that bind to the receptor proteins on the surface of cancer cells in a very specific way. Therefore, if the liposome meets the receptor of cancer cells, it identifies them and binds to the cancer cells through its surface proteins, and then it can transfer its contents to these cells.

One of the anticancer drugs used in this way is "Anthracycline". This drug stops the rapid growth and division of cellsIt helps. Considering that anthracycline drug affects cancerous and healthy cells of the body; To create the effect of this drug only on cancer cells, anthracycline is purposefully placed in liposomes that only release the drug in contact with cancer cells, thus avoiding the side effects of the drug on healthy cells. .

Treatment of fungal infections

Liposomes can be used as carriers of drugs such as Amphotericin B. This drug is used to treat fungal infections. The drug amphotericin B has very effective properties to eliminate fungal infections, but its use is limited due to the toxicity it causes to the nervous system.

Using liposome to carry and encapsulate this drug helps to prevent the drug from having destructive effects on the nervous system and reduces the risk of drug toxicity.

In addition, liposomes usually attack mononuclear phagocytic systems. Some fungi live in phagocytes, so liposomes are a good option for carrying antifungal drugs.

Treatment of parasitic infections

Liposomes are ideal carriers for drug release and enable targeted drug delivery to a specific area of ​​the body. For example, a parasitic infection caused by a macrophage, such as Leishmania, would normally cause a fatal and dangerous condition for the body, and the drug used to fight this infection may not be able to work. , because the toxic dose of the drug for healthy cells is higher than the effective dose of the drug for the infectious agent.

Drug delivery with liposome is a suitable solution for this type of infections. Since liposomes normally identify macrophages as a target, therefore, in the case of carrying an antiparasitic drug, liposomes will be able to deliver the drug to the target by reducing toxicity and increasing the dose (effective dose).

Figure 8: Leishmania macrophage

Treatment of bacterial infections

Considering that antibiotics are usually taken orally, there is less need to use liposomes for this class of drugs. Currently, the use of liposomes is only for antibiotics that are potentially toxic to the body. In the treatment of bacterial infections, oral and injectable antibiotics are used more often than antibiotic-carrying liposomes.

However, some antibiotics are used to reduce the toxicity of the majority of liposomes, including Ribavirin and Azidothymidine.

Gene Therapy

Research on liposome delivery systems is expanding in various fields, including vitamins, minerals, and even gene therapy. Using targeted liposomes, even DNA can be delivered to specific tissues. If the liposome carries functional gene DNA, upon entering the cell, the gene can be transcribed by the cell and produce the protein it encodes for. With the production of protein in the cell, a specific function and characteristic is revealed in it. This process may soon be used to alleviate various genetic diseases.

Image 9: Gene transfer through liposomes

Other industries are producing liposomes for various uses. Since a liposome is essentially a small cell, it is biodegradable over time but can still carry an aqueous solution in a protected manner. Scientists are trying to use this property to create liposomes that can perform complex tasks. Some of these applications include the delivery of nutrients to crops using liposomes as tiny machines. If the right functional constructs, or DNA and corresponding proteins, are put into the liposome, it essentially becomes a tiny living cell that can be programmed to perform various actions. It is not yet possible to create commercial versions of this product, but research in this field is being done in different laboratories. Liposome-like structures

In addition to liposome structures, structures similar to it have been produced to transport drugs and other compounds in the health and food industries, which in some cases have advantages over liposomes, including these structures can be called "Niosomes". ) and "phytosomes" (Phytosome) mentioned. Niosomes are vesicles made of non-ionic surfactants that are formed by hydration of cholesterol. Cholesterol in these compounds increases their strength and hardness, and on the other hand, the presence of non-ionic surfactants gives electrical charge to niosomes and increases the loading of different compounds in these particles.

Phytosomes, as the name suggests, are made from plant compounds. Phytosomes are actually lipid nanocarriers that are produced from the connection between phospholipid and polyphenols in organic solvents.