Liposomes: A Novel Drug Delivery System: An Overview

Nikita R. Nikam*, Priyanka R. Patil, Mr. R. R. Vakhariya, Dr. C. S. Magdum

Rajarambapu College of Pharmacy, Kasegaon, Tal- Walwa Dist- Sangli, Maharashtra

*Corresponding Author E-mail: nikitanikam@gmail.com

ABSTRACT:

The search for liposomes or lipids was performed on self-generated bilayer lipid hydrations. The liposome drug delivery system has played an important role in the formation of powerful drugs to improve treatment. Recently, the symptoms of liposome formulations decrease symptoms and increase conservation at the target site. Liposomes are also used in cosmetic formulations. Liposomes are described in terms of physical, chemical and biological parameters. New developments in this area are the specific binding properties of agglutinating liposomes with target cells such as tumor cells and specific molecules in the body. This review will help researchers working in the field of lymphocytosis. Distribution this article provides an overview of the drug delivery system in the form of liposomes. He focused on classification, mechanisms, types of comedic liposomes and applications on liposome drug delivery systems.

KEYWORDS: Liposomes formulations, lipid bilayer, Characterization, Cosmetics.

INTRODUCTION:

Antineoplastic cytotoxic agents for the vitamins of tumor cells also affect normal cells. Indeed, their low index of improvement (TI) means that the dosage essential to obtain the effect of the tumor is toxic to normal cells. These drugs are targeted at a particular site (diseased sites), so their toxic effects are reduced to less than one tissue¹. Therefore, the most effective drug delivery system administered at the targeted site is required. The support of nanoparticles, microparticles, polysaccharides, conferences and liposomes can be used to monitor specific sites.^2-3

When phospholipids are extracted in water, they automatically form a closed structure and as the membrane bilayer phospholipid in internal aqueous environments, this system is called liposomes⁴. Generally, the liposomes are fixed in the form of spherical flasks with a particle size ranging from 30 nm to several micrometers. Liposomes are widely used as carriers for countless molecules in the cosmetic and pharmaceutical industries.

In addition, the agrifood industries have studied the use of liposomes encapsulation to increase the number of delivery systems that can compensate for volatile compounds (e.g., antimicrobials, antioxidants, flavorings, and bioactive components) and preserve them efficiency. Liposomes can trap hydrophobic and hydrophilic compounds avoid disturbing the detached configuration and get stuck on specific targets.

Cosmetic is basically an active ingredient in cosmetic products that may contain medicinal benefits such as drugs or medicines⁵. The use of racks in products mainly works in five types: purification, decoration, care, hydration and protection that will help beautify the skin. Career technology, which includes nanoparticles such as liposomes, solid lipids, nanoparticles, niosomes, etc. The drugs help in the absorption, absorption and reduction of toxicity caused by high doses.⁶The main reason for doing liposome research is that the fact that liposomes can mimic biological cells can be mainly attributed to liposomes. This means that liposomes are extremely biocompatible, i.e. enzyme, antibacterial, antiviral, antiparazine, fungicide, transdermal transporters, diagnostic tools and a subsidiary for vaccination.⁷

History:

After testing and analyzing phospholipids in water under the electron microscope D. Bungham and his colleague R. W. The first description of liposomes was described by Thorn in 1964. They discovered that phospholipids are automatically defined as they are called "bag-shaped”. Gerald Weissman, a close associate, should be called structure, called liposomes, which they later defined as "microscopic capsules composed of one or more lipid bilayer". This research focused on a large number of searches. The substances used in liposomes are widely used and include the drug delivery system for cosmetics.⁷

Liposomes are designed to achieve the following optimized properties:

1. Control and control of drugs without drugs

2. Quickly overcome the clearance of liposomes

3. Intracellular distribution of drugs

4. Ligand-targeting liposome receptor-mediator endocytosis

5. Publication triggered

6. Nucleic acid and DNA distribution⁸

Classification of Liposomes:

Figure 1: A simplified illustration production methods of Liposomes⁷

Liposomes are classified on the basis of: ^{4, 9}

1. Structure

2. Method of preparation

3. Composition and Application

4. Conventional liposome

5. Specialty liposome

Classification Based on Structure:

Table 1: Vesicle Types with their Size and Number of Lipid Layers

Vesicle Type	Abbreviations	Diameter Size	No. of Lipid Bilayer
Unilamellar vesicle	UV	All size range	One
Small Unilamellar vesicle	SUV	20-100 nm	One
Medium Unilamellar vesicle	MUV	More than 100nm	One
Large Unilamellar vesicle	LUV	More than 100nm	One
Giant Unilamellar vesicle	GUV	More than 1 micro meter	One
Oligolamellar vesicle	OLV	0.1-1 micro meter	Approx. 5
Multi vesicular vesicle	MV	More than 1 micro meter	Multi compartmental structure

2. Based on Method of Preparation

Table 2: Different Preparation Methods and the Vesicles Formed by these Methods

Preparation Method	Vesicle Type
Single or oligolamellar vesicle made by reverse phase evaporation method	REV
Multi lamellar vesicle made by reverse phase evaporation method	MLV-REV
Stable plurilamellar vesicle	SPLV
Frozen and thawed multi lamellar vesicle	FATMLV
Vesicle prepared by extrusion technique	VET
Dehydration- Rehydration method	DR V

3. Based on Composition and Application

Table 3: Different Liposome with their Compositions

Type of Liposome	Abbreviation	Composition
Conventional liposome	CLs	Neutral or negatively charge phospholipids and cholesterol
Fusogenic liposome	RSVE	Reconstituted sendai virus envelops
PH sensitive liposomes	-	Phospholipids such as PER or DOPE with either CHEMS or OA
Cationic liposome	-	Cationic lipid with DOPE
Long circulatory liposome	LCL	Neutral high temp., cholesterol,5-10%PEG,DSP
Immuno liposome	IL	CL or LCL with attached monoclonal antibody or recognition sequences

4. Based Upon Conventional Liposome:

1- Stabilize natural lecithin (PC) mixtures

2- Synthetic identical, chain phospholipids

3- Glycolipids containing liposome

5. Based Upon Specialty Liposome:

1- Bipolar fatty acid

2- Antibody directed liposome.

3- Methyl/ Methylene x- linked liposome.

4- Lipoprotein coated liposome.

5- Carbohydrate coated liposome.

6- Multiple encapsulated liposome.

Figure 2: Illustration of the basic form the lipid bilayer forms in an aqueous solution⁷

Mechanism of liposome preparation:

Liposomes are at the origin of phospholipids, an amphipilic molecule (hydrophilic head and hydrophobic tail). The hydrophilic segments are mainly water-soluble phosphoric acid molecules, while there are two fatty acid chains in the hydrophobic region, where there are 10 to 24 carbon atoms and 0 to 6 double bonds in each series^{1, 10}^.

When these phospholipids are dispersed in an aquatic environment, they form lamellar leaves so that if the polar group of the head is on the aquatic side of the aqueous zone, the fatty acid groups face each other and are eventually formed like structures called liposomes. The polar part remains in contact with the aquatic region with the protection of the non-polar zone (centered on the surface of the flag)^{1, 11}.

Mechanism:

There are several methods by which liposomes act inside and outside the body, they are:

1- The liposome connects to the cell membrane and appears to release its contents into the cell.

2- Sometimes they pass through the cell and their phospholipids are included in the cell membrane through which the drug blocked inside is released.

3-    In the case of phagocytic cells, the liposomes are removed, the walls of the phospholipids are administered by organs called Liposomes and active drugs are released^{4, 12}.

Steps involved in liposome activity during drug administration:

1. Endoscopy: Absorption between liposomes in cell membranes causes contact on the cell membrane.

2. Endocytosis: Pasteurization of liposomes on the surface of the cell and wastewater and insertion into liposomes.

3. Fusion: The lipidyl cell fibers with lipid cell membrane and lipid bilayer fusion with lipids interfere and the liposomal content in the septalizem is directly distributed.

4. Lipid exchange: Lipid transfer proteins in the cell membrane easily identify liposomes and allow lipid exchange due to the similarity of the liposomal lipid membrane with the phospholipids of the cell membrane.⁸

Method of liposome preparation and drug loading:

The following methods are used for the preparation of liposome:

1. Passive loading technique

2. Active loading technique.

Passive loading techniques include three different methods:

1. Mechanical dispersion method.

2. Solvent dispersion method.

3. Detergent removal method.^13-14

Mechanical dispersion method:

Sonication:

Sonication is probably the most widely used method for creating an SUV. Here, MLV, Sonication is performed without a bath-type sounder or probe sounder in an inactive environment. The main drawbacks of this process are the presence of a very low internal volume / disability efficiency, the possibility of compiling phospholipids and compounds, the elimination of large molecules, probe scores, and metal pollution MLV with SUV¹³.

There are two Sonication techniques:

A) Probe Sonication:

The note of the sonicator is direct indirect dispersion in the liposomes. The energy input into the lipid dispersion is much higher in this method. The energy connection at the tip generates local heat; therefore, the texture must be mixed with water / ice during plowing. Up to 1H, up to 5% of lipids can be de-activated. In addition, with the sonicator probe, Titanium will be released and the solution polluted.

B) Bath Sonication:

The dispersion of liposomes in the cylinder is placed in a sniper bath. Controlling the temperature of the lipid dispersion is generally easy in this process, against the Sonitake using an active tip. Ultrasound treated material can be stored in sterile texture, under probe units or in an inert environment.^15.

French pressure cell (extrusion):

French pressure cell involves the extrusion of MLV through a small orifice¹³. An important feature of the French press vesicle method is that the proteins do not seem to be significantly pretentious during the procedure as they are in sonication. An interesting comment is that French press vesicle appears to recall entrapped solutes significantly longer than SUVs do, produced by sonication or detergent removal¹⁶.

The method involves gentle handling of unstable materials. The method has several advantages over sonication methods. The resulting liposomes are rather larger than sonicated SUVs. The drawbacks of the method are that the high temperature is difficult to attain, and the working volumes are comparatively small (about 50 mL as the maximum)^16-17.

Freeze-thawed liposomes:

SUVs are slowly frozen and thawed gradually. Short-term sonication disperses the collected ingredients in the LUV. Due to the fusion of SUVs in the freezing and thawing processes, it is a question of creating Unilamellar Vesicles. This synthesis is strongly limited by the increase in phospholipid concentration and the increase of the ionic strength of the medium. 20 to 30% of insusction effects were received^18-19.

Solvent dispersion method:

Ether injection (solvent vaporization):

The soluble lipid solution in the diethyl ether or ether-methanol mixture is gradually being injected to aqueous solution of the material filled with temperature ranging from 55 ° C to 65 ° C or less. Liposomes are formed by removing the ether below the vacuum. The main misuse of the technique is that the population is uniform (70 to 200 nm) and the appearance of frozen compounds in organic solvents in high temperatures^20-21.

Ethanol injection:

The lipid solution of ethanol is rapidly exposed to a large buffer. Once MLVs are created, abuse of this method is that the population. Liposomes are very thin, it is difficult to remove all the ethanol because they are formed in the agozotope with water and the probability of being inactivated in various biologically active macromolecules is the slightest presence of ethanol²².

Detergent removal method (Dialysis):

The detergents used on their severe microdel concentration (CMC) are used to dissolve the lipids. Detergent detaches, closes in measure phospholipids, and finally creates Eluvi. Detergent was removed by dialysis^23-24. A commercial device called Lipopoere (Dicema AG, Switzerland), which is a version of Dialysis System, is available to remove detergents. Dialysis bags can be widely used in detergent-free buffer (balanced dialysis) dialysis²⁵.

Detergent removal of mixed micelles (absorption):

Get detergent absorption by moving a mixed mile solution with Bead Organic polystyrene absorbers such as XAD-2 Mani and Bio-Modes SM2. The biggest advantage of using detergent absorbers is that they can remove low CMC detergents, which do not completely reduce.

Liposomes: Novel Approach in Cosmoceuticals:

Now one day people are searching for products that will provide maximum returns Minimal effort This kind of cosmetic search is not only for females but also for male Products are cosmetics, which are products that are designed for the body Clean up, beautify or make changes and enhance attractive features⁶.

Liposomes are used in most aquatic systems. Due to fragrances, botany and virus disinfection, lipstick, deodorants, antiperspirants, and body spray, 20-30 microspheres use polymer structures in liposomes. The loss of liposome is the loss of oxidation and deformation or structure. This can be solved by optimizing the storage position of this problem or using anti-oxidants in fraudulent and fraudulent cases²⁶.

Benefits of using liposome in cosmetics:

The main benefits of using liposomes are they are able to nourish the skin Collagen production also helps to improve the flexibility of the skin. The use of liposomes gives benefits in many ways by increasing the stability, Action Restore, Biodegradability, Biocompatibility and Extended and Skinny Skin Releases. The uniformity of the structure with its small size and skin makes it easy to access fixing skin on the outer layer of the skin also helps in the skin's substrate Epidermal skin of skin and frozen drug in the skin layer. At the same time, the problems rapid expulsion of medicines can also solve flammable sunlight products Liposome-enveloped UV filters are water-resistant.²⁷

Characterization:^28-37

A. Biological Characterization:

Table 3: Biological Characterization Parameters and Instruments used for analysis

Characterization Parameter	Instrument for Analysis
Sterility	Aerobic/anaerobic Culture
Pyrogenicity	Rabbit fever response
Animal Toxicity	Monitoring survival rats

B. Chemical Characterization:

Table 4: Chemical Characterization Parameters and Instruments used for analysis

Characterization Parameter	Instrument for Analysis
Phospholipids concentration	HPLC/Barrlet assay
Cholesterol concentration	HPLC / cholesterol oxide assay
Drug concentration	Assay method
Phospholipids per oxidation	UV observance
Phospholipids hydrolysis	HPLC/ TLC
Cholesterol auto-oxidation	HPLC/ TLC
Anti-oxidant degradation	HPLC/ TLC
PH	PH meter

C. Physical Characterization:

Table 5: Physical Characterization Parameters and Instruments used for analysis

Characterization parameter	Instrument for analysis
Vesicle shape, and surface morphology	TEM and SEM
Vesicle size and size distribution	Dynamic light scattering, TEM
Surface charge	Free flow electrophoresis
Phase behavior	DSC, freeze fracture electron microscopy
Percent capture	Mini column centrifugation, gel exclusion
Drug release	Diffuse cell/ dialysis

APPLICATIONS:

Site-avoidance delivery:

Corticobacterial cytotoxicity may be considered as a general remedial index (TI) in normal tissues. In such cases, TI may be modified by encapsulating liposomes to normal cells by reducing drug delivery. Free doxaryribicin has a severe adverse effect on heart disease, but when it is prepared as liposomes, reduces the poisoning without any change in therapeutic activities.^{1, 38-39}.

Site specific targeting:

The distribution of large quantities of medicines to the desired (diseased) site can be achieved by site specific targeting by reducing the normal tissue medication. In order to obtain safe and effective therapy, the drug's active and inactive targets can both be used to enforce the drug in liposomes.³⁹.

Intracellular drug delivery:

Cytosol (which drugs are present in the receptors) strengthens the drug, can be used by the liposomal drug delivery system. N- (Phosphonacetel) -L-Aspartate (Pala) usually worsens in the cell. After overlapping liposomes, such medicines show more activity than ovarian tumor cell lines, rather than free medicines.⁴⁰.

Sustained release drug delivery:

Liposomes can be used to provide medication continuously, which requires long-term plasma concentration on therapeutic levels to get the optimum therapeutic effects. Drugs such as cytosine arbinides can be stored in continuous liposomes and increase the amount of drug free withdrawal in the Vivo.⁴¹.

Intraperitoneal administration:

Intra-peritoneal (IP) can be administered by administering developed tumor medicines through the IP and treated cavity. From there, there is a relatively low density of medicines in the disease that results from accelerated cavity of medicines. However, compared to free medicines, liposomal incontinence medicines have a lower clearance rate and can be provided with maximum amounts of medicines for prolonged on target site.^42-43.

Immunological adjuvant in vaccines:

Liposomes can be enhanced by an antipsure to increase the depression response. Depending on the antibiotic lipophilic, the liposome may insert antibiotics in the water bowl or include it in the billiards. Liposomes have been used as the first immunological agents to increase the immunity response to diphtheria toxide⁴⁴.

Pulmonary Application:

The distribution of liposomes has been explored as a target selection option for systemic administration of astrophatic and antigenic compounds and targeted antibiotics lung infections.

Liposomes are useful tools for the distribution of the lungs because of the density of their waste; the waste products are more viable for airwaves. Their biodegradability Long-term lung home stays in danger from allergies or other side effects^45-46.

Cancer Therapy:

Cytotoxic medicines can generally be distributed throughout the body, normal and hazardous cells can die, which can lead to various toxic side effects. The use of these drugs in liposomes increased the life of the symposiums, the increase in the number of infected tissues, the protection of medicinal metabolism, the replacement of the drug tissue, and in mononuclear phagocyte cells (increased liver, spleen and bone-enhancing organisms increased in the medulla) and decreased kidney, myocardium and brain To fall To target the tumor, liposomes must be able to release the blood and enter the tumor⁴⁵.

CONCLUSION:

Many drug peddlers who are highly effective and have low heritable signs so keep targets on the diseased sites using the liposomal drug delivery system. Medicines containing liposomes can be significant altered pharmacokinetics in the encapsulated. The effectiveness of liposomal formulation depends on its ability to distribute phosphorus on prolonged targeted sites and simultaneously reduce its toxic effects. These events will hopefully protect against future overlapping and unrealistic ideas and assurances, and liposomes will move forward in another high productive and innovative phase of research. From this article, we've completed or understood all the information about liposomal drug delivery systems, classification, methods of preparation and their applications.

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Received on 27.01.2020 Modified on 18.02.2020

Asian J. Pharm. Res. 2020; 10(1):23-28.

DOI: 10.5958/2231-5691.2020.00005.2