INTRODUCTION:

Nanotechnology is a field of research and development that involves a wide range of fields, including the production, processing, and use of materials or devices of one or more sizes in a nanometre range. Nanotechnology is a foremost science that has already influenced many fields, such as agriculture, medicine, cosmetics, and food¹. In addition, nanotechnology in the field of medicine is being used to gain an understanding of how the physicochemical properties of nano-metric materials can change the composition and quality of medicines. The word liposome is obtained from two Greek words i.e. 'Lipos' meaning fat and 'Soma' meaning body², The liposome can be composed of various sizes by unilamellar or multilamellar, and its name is related to its building blocks of phospholipids.

Liposomes were first characterized by the British hematologist Dr. Alec D Bangham in the year 1964, at the Babraham Institute in Cambridge. It was noticed when Bangham and his co worker R.W.Horne were verifying the institute’s new electron microscope by adding negative stain to dry phospholipids. A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane^3,4.

Liposomes can be filled with drugs, and used to deliver cancer drugs and other diseases. Liposomes are usually comprises of phospholipids, molecules that have a head group and a tail group. The head is drawn by water, and the tail, made of a long chain of hydrocarbon, is opposed by water. Liposomes are used for drug delivery because of their exclusive properties⁵. In fact, they can contain a wide variety of hydrophilic and hydrophobic diagnostic and therapeutic agents, provide greater drug load with particles and protect encapsulated agents from metabolic processes. Liposomes entangle DNA is one of two mechanisms that have led to their separation such as cationic liposomes and pH-sensitive liposomes⁶. Cationic liposomes are well-charged liposomes that combine with negatively charged DNA molecules to form a steady complex where as the later liposome is lipid compositions that can be diminish when the external pH is changed. Now a day’s these are very useful model, reagent and tool in various scientific disciplines like mathematics, theoretical physics, biophysics, chemistry, colloidal science, biochemistry, and biology. Another interesting property of liposomes is their natural ability to targeting⁷. ‘Targeting’ is classified into two categories. One is ‘passive targeting’ with a bulk recognition mechanism, in which the targeting is initiated by altering the bulk structural characteristics of the carrier such as its hydrophobicity, hydrophilicity, the charge density, the fluidity, softness, and the size of the carrier⁸. Second is ‘active targeting’ which is acquired by a molecular recognition mechanism. In this mechanism, the targeting is achieved by recognition at the molecular level, through direct and specific interaction between a specific recognition site on the liposomal surface and a receptor on the cytoplasmic membrane of the target cell. When liposomes are introduced into the body, primary tissue distribution builds upon a passive targeting mechanism⁹. However, when the liposome and target cell approach each other with a very short distance between them an active targeting mechanism becomes governing the process. Therefore, active targeting is more eminent and promising than passive targeting¹⁰.

Figure: 1 Mechanism of liposomal action

At the initial stage of the liposome with cell membrane interaction, liposome may non-specifically or specifically attach to the surface of the cell¹¹. Non specific attachment is an electrostatic or hydrophobic interaction where as specific attachment is a receptor-ligand or antigen-antibody interaction. Pursuing such binding the liposome are entered into the cell by the mechanism of endocytosis (cellular process where substances are brought into the cells) followed by the enzymatic digestion of the liposome in the intracellular component¹².

Fundamental constituents of liposome:

Liposome are globular lipid bilayers of 50 to 1000nm in diameter which serves as a convenient delivery vehicle for biologically active compounds. There are a number of structural components of liposomes out of them two components are most important:

Phospholipids:

Phospholipids are the leading structural component of biological coverings and the most common phospholipid is the phosphatidylcholine (PC) molecule. Particles of PC are insoluble in water and they also align themselves closely in order to minimize the adverse action between the bulk aqueous phase and the long chain hydrocarbon fatty acids. Glycerols including phospholipids are generally used component of liposome formulation. Some commonly used phospholipids are lecithin, cephalin, phosphatidyl cerine, phosphatidyl glycerol etc¹³.

Cholesterols:

It does not form a bilayer construction by itself but is able to included into phosphor lipid membranes in very high concentrations. Due to the high solubility of the cholesterol, phospholipid liposome has been used to both hydrophobic and definite head group interaction¹³.

Method of preparation of Liposome:

Materials required for liposome includes

· Phospholipid like lecithin or any other.

· Distilled water.

· Cholesterol.

· Tricine buffer (pH: 7.4): 2mM tricine, 0.34M mannitol, 19mM Sodium Chloride, 2mM Histidine, 0.1mM EDTA. Phosphate buffered saline (PBS pH: 7.2): 134mM NaCl, 2.5mM KCl, 4.3mM Na₂HPO₄, and 1.46mM KH₂PO₄.

· Methanol.

· Acetone.

· Chloroform.

· Diethyl ether.

· Ethanol.

Some of the frequently applied approaches for the synthesis of liposome are

Extrusion technique:

In this method various pore-size of the filters are operated, which structurally modifies to large unilamellar vesicles to nanoliposomes. A high pressure induced extrusion of vesicles through polycarbonate filters. A mini-extruder set 0.5mL gas-tight syringes are widely used in this technique¹⁴.

Figure 2 An Extruder

Sonication:

Sonication is commonly used method for the formation of liposome and nanoliposomes. Sonication is a simple procedure for decreasing the size of liposomes and generation of nanoliposome. Probe sonication works with handling hydrated vesicles for few minutes with a titanium-tipped probe sonicator¹⁴.

Figure 3: Probe Sonicator

Microfluidization:

This process uses a divided pressure stream into passing each part across a tiny aperture and leading the flows to each other inside the cavity of microfluidizer. High pressures results direct flow of stream through micro channels result in cavitation in company with shear and impact inside the interaction chamber decreases particles size of the liposomes¹⁵.

Figure 4: Microfludizer

According to liposome work and intracellular mechanism of delivery it can be of five types

Conventional liposome:

These are the first discovered liposome used in the pharmaceutical application consists of natural phospholipids like egg phosphatidylcholine, sphingomyelin.

pH sensitive liposome:

These are designed based on the concept of viruses which merge with the endosomal membrane delivering their genetic material to the cytosol before reaching the lysosome.

Cationic liposome:

These are the mixers of cataionic lipids with DNA and delivering them to the cells. This develops the structures of collectives which composed of DNA and cationic lipids.

Immune liposome:

The reconstitution of antigens into liposomal membrane or their incorporation into the interior water core of the liposome would cause the enhancement of immune response.

Long circulating liposome:

This type of liposome can be obtained by when polyethylene glycol is covalently bound to the phosphor lipids. It has been experimentally verified that blood circulation time can be extended by using this type of liposome¹⁵.

Merits of liposome:

· Liposome can make complex with both positively and negatively charged molecules

· It gives protection to the DNA from degradation process.

· It can be targeted to the specific cells or tissues¹⁶.

Demerits of liposome:

· The cost of the production is high

· Leakage or fusion may be occurred with encapsulated drug molecules

· Used phospholipids may undergoes oxidation or hydrolysis

Applications:

· Liposome show less toxicity with the encapsulated drug, so many anticancer drugs encapsulated with liposome and specifically it can be targeted to the specific cancer cell or tissue.

· Since liposome are digested by phagocytic cells after intravenous administration several parasitic bacteria’s which normally reside in the cells can be targeted and diagnosed¹⁷.

· Liposome are used for the treatment of neonatal jaundice.

· Liposomal antibiotics, steroids, infusions are now a days available in terms of vaccine application.

· Antifungal drug Amphotericin B shows better result in liposomal drug delivery¹⁸.

CONCLUSION:

The harmonious inputs from the colloidal science, chemistry, biology and medicine has proved the successful development of liposomal drug delivery and the strong theoretical and experimental works which have been developed assured new renovations and products. Only time will speak which of the above application and considerations will be prove successful. With the progression of other technologies in medicine, the area of liposome will be a more impetus and reliable platform for the development of useful bio products especially in terms of medical diagnostic and public healthcares.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGEMENT:

The authors are thankful to the teaching and non teaching staffs, Lab Heads of Roland Inst. of Pharmaceutical Sciences for their cooperation.

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Received on 24.12.2021 Modified on 10.03.2022

Asian J. Pharm. Tech. 2022; 12(4):361-364.

DOI: 10.52711/2231-5713.2022.00056