INTRODUCTION:

A crystalline solid contains a structural lattice which runs in all the three dimensions and has a positional and orientational order whereas, a liquid does not contain a lattice or any structure. Liquid Crystals are defined as the state of matter existing between the liquid and the crystalline solid. They possess fluidity like liquids and have a specific arrangement of molecules like a lattice as it is observed in crystals. Liquid Crystals are characterized^[1]by the partial or complete loss of positional order in crystalline solids, while retaining the orientational order of the constituent molecules.

Liquid crystals is a unique state shown by organic compounds. Since, liquid crystals are intermediate between solids and liquids, they are also called as mesophases. Liquid crystals are anisotropic; which means they have different chemical and physical properties in different axes. It is important to note that^[1] not all anisotropic materials are liquid crystals but all liquid crystals are anisotropic compounds. Due to anisotropy of liquid crystals, they also exhibit birefringement i.e. having two refractive indices. Having an anisotropic molecular shape associated with polarizability is the basic requirement for liquid crystals.^[2]

Liquid crystals are classified into two types according to their method preparation:

1. Thermo tropic liquid crystals

2. Lyotropic liquid crystals

Thermotropic Liquid Crystals:

The liquid crystallinity of these compounds are a function of temperature.^[12] If the temperature is too high, it will destroy the ordering of the liquid crystals converting it into normal anisotropic form. On the other hand, at very low temperatures the materials will form conventional crystals.^[6,11] Unlike lyotropic substances, they do not require solvent for formation.^[4,8] There are three types of Thermotropic LCs:

a. Nematic phase:

In Greek, nema means thread.^[3] Under a microscope, when using polarized light, Nematic LCs appear thread-like structures.^[7] In this phase, the rod-shaped organic molecules have no positional order but they align themselves to have long range direction order.^[3] Their physical properties like refraction index, permeability dielectric constant, etc. are anisotropic^[7],[9]. These crystals are widely used in electronic display.

b. Smectic phase:

These are found at even lower temperatures than nematic phase. The word smetics means cleaning or rather having a soap like properties.^[5] The long axes of all the molecules in a particular layer are parallel to one another and perpendicular to the plane of layer. True to its name, the layer slides over one another similar to that of soap’s. This phase is viscous, fluid and ordered.^[7]

c. Cholesteric phases:

This phase is called cholesteric phase because it was first discovered in cholesterol derivatives.^[6] This arrangement to extent is a combination of nematic phase and smectic phase. The layers are able to slide over one another and are parallel to each other; a property similar to nematic phase. The layers are also perpendicular to the plane which is similar to the smectic phase.^[8,10] Cholesteric phase is only observed in chiral compounds hence, it is also called Chiral phase.^[6]

A vesicle is a small, intracellular, membrane-enclosed sac that stores or transports substances within a cell.^[13]Within a living, the vesicle is separated from cytosol by a unimembrane or multimembrane of phospholipid. Various types of vesicles are formed in the cells for functions like storage, transportation, digestion of cellular waste. For example, lysosomes which contains digestive enzymes like proteases, glucosidases and sulfatases.

Vesicular carriers are drug delivery nanoparticles formed by amphiphilic polymer backbone, commonly of phospholipids in which the active pharmaceutical ingredient is enclosed.^[13]There are many such vesicles are present on which extensive research is carried out. Out of such vesicles, the one with great potential is Liposomes.

Discovery of Liposomes:

The term liposome arises from two Greek words, lipo meaning fat and soma meaning body. The discovery of liposomes was made by a British haematologist A.D. Bangham in the year 1961 at the Babraham Institute in Cambridge. He and his colleagues reacted egg lecithin with water and the reaction produced new structures. They also observed that the strong positive birefringence of lecithin in water dispersion was almost turned negative when added into the lipid lamellae of the increasing amounts of long chain anions or cations.^[14]These lipid vesicles were initially smectic phases but were later named liposome.^[15]

Classification of Liposomes:

Based on their structure:

Size and number of bilayer affect the amount of drug that can be encapsulated into the vesicle. According to the number of bilayer, liposome can be classified into two types: (1) Unilamellar vesicles (UV) and (2) Multilamellar vesicles (MLV). Unilamellar vesicles have a single phospholipid bilayer and usually enclose an aqueous medium. They are further classified into (1) Small unilamellar vesicles (SUV), (2) Large unilamellar vesicles (LUV)^[28,29] and (3) Giant unilamellar vesicles (GUV)^[35]. Small unilamellar vesicles have a diameter of 2-50 nm, large unilamellar vesicles have a diameter 100-1000 nm and giant unilamellar vesicles have the biggest diameter (>1000 nm)^[30,31,35].

Multilamellar vesicles have an onion structure i.e. multiple phospholipid bilayer. Generally, several unilamellar vesicles will form in the inner layer of small ones to form a multilamellar structure of concentric layers each separated by layers of water, having a general size greater than 500nm^[29]. Apart from these two main types of liposomes, there is also Oligolamellar vesicles with a diameter of 100-1000 nm. A multicompartmental vesicle called Multivesicullar vesicle have a size greater than1000nm^[32,33,34].

Applications of Liposomes as Drug Delivery Systems:

Traditional drug delivery systems face complications like inefficient biodistribution, indifferentiated body tissue targeting, and nonspecific drug delivery. In hopes to overcome this drawbacks of conventional drug delivery system, liposomes with key modifications were developed^[27]. Many drugs show a very small therapeutic window, and many literature exists stating that drugs having a small therapeutic window when used with suitable carrier that can alter the delivery of drugs, showed less toxicity or either a greater efficacy.

Antitumor activity:

Anthracyclines, drugs derived from the Streptomyces bacterium, are a class of potent and widely used cytotoxic drugs. They inhibit DNA and RNA synthesis by creation iron mediated free oxygen radicals, damaging the DNA and cell membranes, and also inhibit topoisomerase II. Thus killing mainly rapidly dividing cells, including but not limited to, tumors. Body cells like hair follicles, GI mucosa, and blood cells, making the use of these drugs very toxic. Doxorubicin hydrochloride is marketed widely used anthracyclines. Liposomal delivery has proved to be very effective when doxorubicin hydrochloride is loaded into liposome and then coated with Polyethylene glycol (PEG). It drastically reduced the its toxicity to the heart as compared to the traditional delivery^[26]. Such type of liposomes wascalled stealth liposomes. It was observed that repeated injections of these liposomes lead to its rapid clearance from the systemic circulation. Injected liposomes elicit an immune response which produces anti-PEG IgM, this increase the blood clearance under certain conditions. Despite all this, a recent report suggest that encapsulated Doxorubicin in PEG coated liposome elicit damage to T-cell independent B-cell mediated accelerated blood clearance phenomenon ^[22,23,24]. The magnitude of the phenomenon depends on the time interval between doses, therefore it is recommended a low injection frequency.

Recently a new class of liposomes have surfaced which successfully overcome the limitations of conventional liposomes. Unlike the traditional liposomes, this new class undergo physical and chemical changes in response to stimuli. Solid tumors have poor vasculature, meaning they have anaerobic conditions which lead to decrease in pH. This decrease in pH act as a stimuli and trigger drug release from the liposomes^[21]. In diagnostic medicine, theranostic liposomes are acrucial development in nanomedicine.

In infections:

Leishmaniasis is a parasitic infection of macrophageswhich affects over 100 million people in tropical regions and is often deadly. The dose of drugs, mostly different antimonials, is not much lower than the toxic one. Liposomes accumulate in the very same cell population which is infected, and so an ideal drug delivery vehicle was proposed^[17]. There are various research was carried out on liposomes in the antifungal therapy. Liposomes as carriers for amphotericin B, foramphotericin B have proved to reduce the toxicity of these drugs and also cause passive targeting as often the fungus exist in the mononuclear phagocytic system^[18,19]. Antiviral drugs like ribavirin, azidothymidine, or acyclovir when encapsulated into liposome also showed reduced toxicity. It is only feasible of highly toxic antibacterials and antivirals to be given by liposomal drug delivery^[20].

Delivery of phytomedicines:

As liposomes are vesicles, they can encase phytomedicines and can be used for oral and topical administration. Since phytomedicines often have more than one pharmacological activity, vesicular encapsulation can be beneficial for targeted drug delivery to the site where the action is desired. This delivery system for phtomedicines can be very beneficial as phytomedicines are already known for their characteristic physicochemical properties, making them difficult to deliver. Also, this method produces less waste undesired effects. Hence, due to the special characteristics of liposomes, it can bypass the hurdles in the phytomedicine delivery^[16].

CONCLUSION:

Liposome are a type of vesicular carrier which entrap drug molecules, and provide targeted drug delivery. Over the years, liposomes have gained the interest of the researchers as an ideal drug delivery system for toxic and potent drugs, all owing to its unique characteristics like great bio-distribution, targeted drug delivery, low dosage and low toxicity. All these characteristics are the reason that liposomes are now used in cancer therapy, as antifungal drug therapy, in delivery of phytomedicines. With high clearance, low toxicity liposome will sure prove itself in the therapeutics as ideal drug delivery system. Extensive research is still being carried out on liposome but many are decisive that liposome is the novel deliver system which will shape the world of therapeutics and pharmacy.

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Received on 03.04.2020 Modified on 19.04.2020

Asian J. Research Chem. 2020; 13(4):287-290.

DOI: 10.5958/0974-4150.2020.00056.5