Transfersomes: A Novel Vesicular Drug Delivery System for Enhanced Permeation through Skin
Madhumitha. V, Dr. S. Sangeetha
Department of Pharmaceutics, SRM Institute of Science and Technology, Kattankulathur-603203
*Corresponding Author E-mail: drsangeetha1978@gmail.com
ABSTRACT:
Transdermal drug delivery systems are showing great improvement in delivering drugs as their advantages overweigh the disadvantages. Transfersomes are vesicular drug delivery systems which are used to enhance the penetration ability of drugs in a non-invasive manner. They have the ability to shrink themselves from 5 to 10 times less than their own diameter and reform in order to pass through a narrow pore. In this review we have discussed about transfersomes , their mechanism to easily penetrate skin by overcoming the barriers present in stratum corneum as well as the methods used in preparation of transfersomes along with their evaluation parameters involved. This newer approach to deliver drugs has got various applications in different fields. Some of their applications include delivery of : Transdermal immunization, NSAIDS, Herbal drugs, Corticosteroids and Interferons. Apart from these they prove to be a great carrier of high molecular weight proteins and insulin in case of diabetic patients. Recently, They are widely studied for their use in treatment of various cancer. Hence in our review, it was observed that transfersomes prove to a be a very good carrier for drugs when compared to liposomal drug delivery system.
KEYWORDS: Transfersomes, skin permeation, Deformable vesicles, Transdermal drug delivery, Non Invasive delivery.
INTRODUCTION:
A transfersome is a tool that can transfer drugs when applied on the targeted site through easy penetration of skin(1-3). An ultra-deformable vesicle which possess an aqueous core surrounded by complex lipid bilayer is its preferred form. The self -regulating and self-optimising properties of transferosomes are because of their interdependency of local composition as well as the shape of the bilayer. They can efficiently pass through various transport barriers and then act as an efficient drug carrier for sustained release of therapeutic agents and non-invasive targeted drug delivery is due to these properties4,5. Flexible elastic lipid-based vesicles such as transfersomes and ethosomes are the two novel vesicular carriers which resulted from the approaches6
Inner layer of each transfersome is comprised of aqueous compartment, which is surrounded by a lipid bilayer having specially modified properties, due to the addition of "edge activators" into the vesicular membrane. Edge activators used widely are surfactants such as sodium cholate, sodium deoxycholate, Span 80, and Tween 807
Fig 1: Transfersomes Structure.
Mechanism of Action:
Upto 0.1mg of lipid per cm2 can be transferred over the skin area through transfersome8 . Transfersomes not only possess unique flexibility but also decreases the threat of complete vesicles rupture in the skin and when applied under non occlusive condition (concentration independent ) across the epidermis, the vesicles are able to follow the natural water gradient9. On reaching a pore, due to self-optimizing deformability, transfersomes have the capacity to change their membrane work reversibly. The passage of transfersomes is highly influenced by the flexibility of their membrane through the skin and their epithelial barrier. Additionally, the flexibility of transfersomes is responsible for the change in their membrane composition both locally and reversibly when pressed against or made to pass through a narrow pore. The flexibility which decreases the risk of complete vesicle rupture in the skin is achieved via a suitable ratio of surfactants10. The rate of drug release and drug deposition is governed by the change in composition of the vehicle and their surface properties11 .
Fig 2: Mechanism of Transfersomes Penetration Elastomechanics.
Propensity of Penetration:
Hence , when lipid solution is replaced by some amount of lipids in a suspension, the chemically driven lipid flow across the skin always decreases.
Flow = Area x Permeability (Barrier) x Force (Trans-barrier) 12.
Fig 3: Mechanism of Transfersomes Penetration Transepidermal water activity gradient.
Limitations of Transfersomes:
1. Transfersomes , because of their predisposition to oxidative degradation are chemically unstable.
2. The adoption of transfersomes as drug delivery vehicles is hindered by another criteria which is the purity of natural phospholipids13,15,16 .
3. The Manufacturing as well as the processing of transfersome is quite expensive17,18 .
Advantages of Transfersomes
1. Transfersomes can deform and go across narrow constriction (from 5 to 10 times less than their own diameter) without quantifiable loss.
2. Their entrapment efficiency is high , it is close to 90 % in case of lipophilic drug .
3. They are made from natural phospholipids as that of liposomes hence are biocompatible and biodegradable.
4. The encapsulated drug is protected from metabolic degradation.14,15,16
Salient Features of Transfersomes :
1. Transfersomes can house drug molecules having solubility of wide range. This is because of their infrastructure which contains hydrophobic and hydrophilic moieties together in it.
2. The high deformability of transfersomes give better penetration of vesicles19.
3. For drugs having both low as well as high molecular weight e.g. analgesic, corticosteroids, anticancer, insulin and albumin transfersomes can act as a carrier.
4. Transfersomes can release their contents in slow and gradual manner hence act as a depot. Both systemic and topical delivery of drugs through transfersomes is possible.
5. The formulation of transfersomes is simple , do not involve lengthy procedure or pharmaceutically unacceptable and unnecessary additives, hence it is easy to scale up20,21,22.
Preparation of Transfersomes:
There are various patented and published procedures available for the preparation of transfersome. General procedure involves mixing of phosphatidylcholine in ethanol with sodium cholate or some suitable surfactant 14,23 .
1. Suspension Homogenization Process:
In this method, an ethanolic soybean phosphatidylcholine is mixed with edge activators of an appropriate amount, e.g. sodium cholate. To this prepared suspension Triethanolamine-HCl buffer solution is mixed to yield a total lipid concentration and then it is sonicated, frozen, and thawed for 2 to 3 times after which they are brought to desired size which is then measured by using photon correlation spectroscopy. Sterilization is done by filtering through a 0.2mm micro porous filter. Dynamic light scattering technique is used to confirm the final vesicle size 24 .
2. Rotary Film Evaporation Method:
Bangham initially invented hand shaking process, which is also known as rotary film evaporator method25. In this method, to organize a thin film, the need of phospholipids and surfactants is essential26,27. A combination of crude solvent such as chloroform and methanol in which a solution of phospholipids and ethanol are organized. For research purpose of multilamellar vesicles, this method is largely been used. After transferring the prepared solution to a round bottomed flask, it is rotated at a constant temperature ( greater than the glass transition temperature of lipids) and pressure. On the walls of the flask, a film of lipids and edge activators is formed. Using aqueous media containing drug the twisted film is hydrated on account of which lipids tend to swell and form bilayer vesicles. By using sonication of the superior vesicles or by extrusion, vesicles of desired size can be obtained28.
3. Thin Film Hydration Technique:
There are three steps involved in this technique:
1. To get thin film of vesicle phospholipids along with surfactants in an organic solvent (such as chloroform and methanol) is dissolved. Heating is carried out above the transition temperature of the lipid. To free the mixture of organic solvent the process is carried out in a rotary evaporator. By placing it overnight in vacuum, any traces of solvent are removed.
2. For one hour with suitable buffer at 60RPM the formed film undergoes hydration. At room temperature, the formed vesicles are left to swell for 2 hours.
3. Using bath sonicator for 30 mins at 50°C or at room temperature the prepared vesicles are subjected to sonication in order to prepare small vesicles. In case of probe sonicator, at 40°C sonication is carried out for 30 mins. By homogenizing the sonicated vesicles through manual extrusion 10 times through a polycarbonate membrane yields of 200nm - 100nm sandwich layer14,16,29.
With unremitting stirring at constant temperature the aqueous solution containing drug is heated. Edge activators along with ethanolic solution of phospholipids is injected dropwise into the aqueous solution. The lipid molecules are precipitated as the aqueous media comes into contact with the solution and form bilayered structures. The process is easy to scaleup, simple and highly reproduceable, hence serves various benefits when compared to other methods30,31.
5. Modified Handshaking Process:
This method is also known as lipid film hydration technique. In the ratio of 1:1 ethanol and chloroform are mixed. In this mixture drug, lipid and edge activators are dissolved. By evaporation the solvent is removed. At temperature above liquid transition temperature (i.e.) 43°C, hand shaking is achieved. with a constant rotation, inside the flask wall a thin lipid film is formed. For complete evaporation of the solvent, the preparation is left overnight. For 15 minutes with gentle shaking the film is hydrated with phosphate buffer and gentle shaking is done at corresponding temperature32.
This method includes exposure to both low and high temperature. The multilamellar vesicles are subjected to alternative cycles for freezing at very low temperature followed by very high temperatures. The prepared suspension is dipped in a nitrogen bath after transferring to a tube at −30°C for 30 seconds. They are exposed to high temperature in a water bath after freezing. This procedure is repeated 8-9 times33 .
In phosphate buffer, the mixed lipids (edge activators, phosphatidyl choline, therapeutic agents) are all blended. Further to obtain a milky suspension it is vortexed. The suspension undergoes extrusion undergoes extrusion through polycarbonate membranes after sonication34.
Optimization of Formulation Containing Transfersomes:
The preparation and properties of transfersomes are affected by various process variables. Therefore optimization and validation are carried out to the preparation procedure. Depending upon the manufacturing procedure involved in the formulation, the process variables are selected. The process variables involved in the manufacturing of formulation are:
1. Hydration medium.
2. Lecithin : surfactant ratio.
3. Effect of various surfactants.
4. Effect of various solvents.
By selecting entrapment efficiency of the drug, optimization was done. The other variables were kept constant during the preparation of particular system 32,35,36.
Characterization of Transfersomes:
Liposomes, niosomes and micelles possess the same characterization as that of transfersomes17 .
1. Vesicle Size, Size Distribution And Vesicle Diameter:
The vesicular shape is studied using transmission electron microscopic studies. The dynamic light scattering (DLS) method or photon correlation spectroscopy gives details on the diameter of the vesicle. Generally, light scattering technique is used to study the size of the vesicle and also the size distribution. Distilled water is used in the preparation of sample . after passing through a membrane filter of 0.2 mm , the samples are diluted with filtered saline37.
2. Entrapment Efficiency:
Amount of drug entrapped in percent of what that is added is called as entrapment efficiency. By using mini-column centrifugation the unentrapped drug is separated. 0.1% Triton X-100 or 50% n-propanol is used for the disruption of vesicles.
Entrapment Efficiency:
Amount Entrapped
--------------------------------------- X 100
Total Amount Added
Hence entrapment efficiency can be determined using these steps38 .
3. Penetration Ability:
Using fluorescence microscopy, the penetration ability of transfersomes can be determined16,39 .
4. Turbidity Measurement:
Nephelometer can be used to measure the turbidity of drug in aqueous solution14 .
5. Degree of Deformability or Permeability Measurement:
Using dynamic light scattering (DLS) measurements, after each pass the particle size and the size distributions are noted. As a standard, the deformability study is done against pure water14,39 .
6. Physical Stability:
Sealed glass ampoules are used to store the drug after determining the initial percentage of entrapped drug in the formulation. The ampoules are placed at three different temperature at least for three months (i.e.) in refrigeration at 4°c ± 2°c , then in room temperature at 25°c ± 2°c, later in body temperature at 37°c ± 2°c. After 30 days to determine the drug leakage, each ampoules containing the samples were analysed. By keeping the initial entrapment of drug at 100%, the percentage drug loss was calculated35,36.
7. Skin Deposition Studies of Optimized Formulation:
The goat skin surface after the end of permeation study of 24 hours is washed 5 times with a solution which contains PBS (pH 7.4) in ratio 1:1 ratio. By washing with water the excess drug present on the surface is removed. Ethanol and buffer solution having pH 7.4 are used to cut the skin into small pieces after homogenization. It is then left at room temperature for 6 hours. The drug content is determined using appropriate phosphate buffer dilutions (pH 7.4) after shaking and centrifuging it at 500 RPM for 5 minutes. Using T test the results are compared with that of the control14.
8. Drug Content:
The drug content is determined using various instrumental analytical methods like modified HPLC using a UV detector. Depending on the pharmacopoeial analytical method, the choice of other parameters reside 35.
9. Number of vesicles per cubic mm:
Dilution is carried out 5 times with 0.9% Nacl solution for non-sonicated transfersome formulations. For further study optical microscope and Haemocytometer can be used. For optimizing the other process variables and the composition, this is an important parameter16.
10. In vitro Drug release:
Before expensive invivo studies are carried out, the formulation is carried out by the information from invitro studies and the time needed to reach steady state permeation along with its flux. By taking the amount of drug entrapped at 0 times as the initial amount, indirectly the amount of drug released is then calculated 14,16.
11. In vitro Skin Permeation Studies:
Modified trans diffusion apparatus is used for this study, whose effective diffusion area is 2.50cm2 and the volume of receiver compartment is 50ml. Goat skin in phosphate buffer solution of pH 7.4 is utilized for performing in vitro drug study. In the calculation of release profile for each aliquot, their correction factors were also considered. By using instrumental analytical technique the samples were analysed32,40.
12. Occlusion Effect:
In case of traditional tropical preparations, occlusion of skin is found to assist the permeation of drug. Whereas, in case of elastic vesicles, occlusion of skin is proved to be have deleterious effect. Movement of vesicles from a dry surface to deep water rich region is due to a mechanism called hydrotaxis (movement in the direction of water) which serves as the major driving force for penetration of skin by the vesicles. Occlusion prevents evaporation of water from the skin and hence affects the hydration forces14.
13. Confocal Scanning Laser Microscopy Study:
Staining of the skin, fixing the tissues in a position and sectioning of cells is found to be a major problem in both electron microscopy and conventional light microscopy. There occur many miscalculation as most of the processing techniques are found to be incompatible with the structures to be examined. All these errors and misinterpretations can be reduced by the use of Confocal Scanning Laser Microscopy (CSLM). In transfersomes, lipophilic fluorescence markers are incorporated. Some markers being used are:
1. Nile red
2. Rhodamine- DHPE (1, 2- dihexadecanoyl- sn- glycero- 3ogisogietgabikanube-Lissamine Tmrhodamine-B- sulfonyl), triethanol- amine salt)41.
14. Surface Charge and Charge Density:
Using zetasizer, the charge density and surface charge of transfersomes can be determined14,16.
APPLICATIONS OF TRANSFERSOMES:
1. Delivery of Anaesthetics:
A. Within less than 10 minutes under appropriate conditions anaesthetics when applied in the form of transfersomes induce a topical anaesthesia. As strong as 80% of pain insensitivity occurs as that of a comparable bolus injection but the effects of transfersomal anaesthetics have longer duration13 .
C. Planas ME et.al., studied on Non-invasive percutaneous induction of topical analgesia by a new type of drug carrier, and prolongation of local pain insensitivity. In their study, local anaesthetics and common analgesics were applied dermally on rats and humans in form of transfersomes. Their permeability and duration of action were studied. Their study shows that transfersomes offers a promising means for non-invasive treatment of local pain as they are direct, topical drug application. The corresponding subcutaneous injection of similar drug quantities are found to have the same effectiveness of dermally applied anaesthetic transfersomes43.
2. Delivery of NSAIDS:
A. In case of NSAIDS, there are some problems like GI irritation, which can be overcome by transdermal delivery of transfersomes. Ketoprofen and diclofenac using transfersomes are already studied for efficacy and it is notable that swiss regulatory agency has already approved ketoprofen formulation44.
B. Sureewan Duangjit et.al., studied the Characterization and in vitro Skin Permeation of Meloxicam-Loaded Liposomes versus Transfersomes. Their study involved transdermal delivery of meloxicam (MX) using liposome and transfersome vesicles and to evaluate their potential use. Skin permeation capacity of MX loaded transfersomes were found to be high when compared to MX loaded liposomes as the MX loaded transfersomes were subjected to many evaluation parameters like particle size, loading efficiency, zeta potential, in vitro skin permeation and stability after preparation. Stratum corneum lipid is disrupted by transfersomes which was clearly indicated by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR). Hence through their study transfersomes can be potentially suitable for transdermal drug delivery system45.
C. Makhmalzadeh et.al., studied on Formulation, characterization and in vitro/ex vivo evaluation of trolamine salicylate-loaded transfersomes as transdermal drug delivery carriers.
The aim of their study was to evaluate the permeability parameters of trolamine salicylate through rat skin using different transfersome formulation. Franz diffusion cell was used to compare it with controls. Preparation technique used is solvent evaporation, whereas for data analysis and for the design of experiment, full factorial design was applied. Hence their study concluded that for trolamine salicylate to permeate through rat skin, the rate limiting step is found to be the portioning from the vehicle into the skin. Transfersomes has improved this rate limiting barrier of trolamine salicylate46.
3. Delivery of Herbal Drugs:
R.Patel et.al., studied on the Development and Characterization of Curcumin Loaded Transfersome for Transdermal Delivery. In their study, for transdermal delivery of curcumin, transfersomal formulation was potentially investigated. The potent anti-inflammatory herbal drug curcumin, has an activity which is similar to NSAIDS during management of pain. On the other hand when administered orally, curcumin due to decreased GI absorption becomes poorly bioavailable. Various process variables such as surfactant ratio, effect of lecithin, effect of surfactants and the effect of various solvents were selected for optimization of the formulation. Hence from their studies it was concluded that permeability of curcumin can be improved in a duration of time using transfersomes formed from PC: span 80 (in the ratio 8:15 mmol )32.
4. Transdermal Immunization:
Soluble proteins like human serum albumin, gap junction proteins and integral membrane proteins can be loaded into transfersomes. Two major significance of this approach are found to be :
1. It gives rise to high IgA levels .
2. There occurs high titer.
3. It can be administered without the need of injections 13.
5. Delivery of Anticancer Drugs:
Newer approaches like transfersomes were tried for cancer treatment especially skin cancer for drugs like methotrexate and favourable results in delivering the drug13,49.
A. Z.Zhang et.al., studied on 5-Fluorouracil-Loaded Transfersome as Theranostics in Dermal Tumor of Hypertrophic Scar Tissue. In this study, they investigated the invivo permeation of transfersomal gel loaded with anti-scarring agent (5-FU) into hypertrophic scars. Rhodamine 6GO, a fluorescent agent is labelled to it and in vitro scar permeation studies were carried out. Through their study, they concluded that transfersomal gel had high permeation depth and rate with greater content retention of agent in scar tissues when compared to PBS gel of 5FU. In rabbits the hyperplasia of ear scars were inhibited for some period by local administration of the agent. Hence from their study transfersomes were shown to be an efficient transdermal drug delivery system50.
B. et.al., studied on Transdermal and lymph targeting transfersomes of vincristine . Vincristine a drug used for treating leukemia and hogkin /non-hogkin lymphoma was chosen. On the contrary, its clinical use has been limited due to its local stimulation and neuro toxicity. Hence the aim of their study was to decrease its side effects as well as increase their curative effects. Ultra-sonic dispersion methods and dry film were used to prepare transfersome loaded with Vincristine. The targeting ability, pharmaceutical properties and pharmacokinetic characters of the Vincristine were determined using a HPLC method. From their study, they concluded that transfersomes have good lymph targeting ability51.
6. Delivery of Corticosteroids:
Another important application of transfersomes is the delivery of corticosteroids. The administered drug dose is epicutaneously optimized, hence the overall safety as well as site specificity of corticosteroids is enhanced by transfersomes. The transfersome loaded corticosteroids show many advantages as they are biologically active at a very low dose when compared to currently used formulation in treating skin diseases23.
Gregor Cevc et.al., studied on Transfersomes-mediated transepidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo. In their study, it was shown that overall drug safety and specificity of topical drug delivery were increased by transfersomes. It is found to show high systematic drug availability as there is an increased dose per area as well as total applied drug dose. Due to superior potential of drug targeting in organ, the transfersomal corticosteroid formulation has an anti-oedema activity exceeding several commercial products52 .
7. Delivery Of Proteins And Peptides:
A. When given through oral route, proteins get degraded easily and is difficult for administration as they are large in size. Subcutaneous injections are chosen widely for administration of proteins into the body. Transfersomes are found to have the same bioavailability as that of subcutaneous injections delivering proteins in suspension. When applied in repetitive epicutaneous manner, transfersomes are found to generate strong immune responses. Using transfersomes as carrier, albumin remains immunologically active even after several dermal challenges 53,54.
8. Delivery Of Insulin:
Subcutaneous injections are generally used to deliver insulin. However insulin can also be administered through topical means on skin in an intact manner by enclosing it in a transfersome carrier. After application depending on the composition of the carrier also the first signs of hyperglycemia are reported after 90 to 180 minutes. Other anti-diabetic drugs like repaglinide are also being studied to improve the skin permeation 56.
9. Delivery Of Interferons:
A. Hofer C et.al., studied on Formulation of interleukin-2 and interferon-alpha containing ultradeformable carriers for potential transdermal application. The aim of his work was to study , formulate and evaluate interferon-alpha containing transfersomes and interleukin 2 . About 75-80% of IFN and IL-2 has been incorporated in transfersomes and were found to be biologically active. From their study it was concluded that the incorporated IFN and IL-2 were in sufficient bioactive form of concentration for the purpose of immune therapy. In cell line model of murine RENCA, these IL-2 and IFN entrapped transfersomes were used in upcoming experiments as a transdermal approach57.
10. Other Applications:
1. Mona Qushawy et.al., studied on Design, Optimization and Characterization of a Transfersomal Gel Using Miconazole Nitrate for the Treatment of Candida Skin Infections. For their study, they chose antifungal drug Miconazole nitrate which is used for the treatment of superficial fungal infection. The objective of their study was to develop a formulation containing transfersomes loaded with Miconazole nitrate as they have low skin permeability which can be easily avoided when formulated with transfersomes as they can overcome skin barrier mechanism. In comparison with a marketed product (Daktarin®cream 2%) the optimized formulation is evaluated for invivo and invitro antifungal activity, pH, viscosity, drug content, spreadability and invitro permeation. From their study it was concluded that the skin barrier can be efficiently avoided using transfersomes58.
2. Sakshi Sharma Dogra et.al., studied on transfersomes as a novel approach for intranasal delivery. Nasal route which has rapid absorption of drug can locally exert the effects of drug. In spite of these advantages nasal route of drug delivery has short residence time of drug in nose and the bioavailability of hydrophilic drugs is very low. These drawbacks can be rectified by using transfersomes, as they have the ability to increase the penetration power of both high and low molecular weight drugs . Hence their study concluded that transfersomes can be used as an efficient penetration of drug in nasal and conventional delivery systems59.
3. Marwa h. abdallah studied on transfersomes as a transdermal drug delivery system for enhancement the antifungal activity of nystatin . The aim of their study is to overcome the poor solubility of nystatin, an antifungal drug and to improve its bioavailability by formulating with transfersome. Rotary evaporation sonication method was used to hydrate lipid film in preparation of transfersomes loaded with Nystatin. Transmission Electron Microscopy is used to confirm the spherical structure of vesicle with prolonged delivery and high stability characteristics. Their study proved transfersomes as a good carrier of nystatin to enhance penetration27.
Table 1:
|
S.No |
Name Of Drug |
Classification |
Inference |
Reference |
|
1. |
Curcumin |
Antibacterial, anti-inflammatory, hypoglycemic, agent |
Better permeation for anti-inflammatory activity |
32 |
|
2. |
Indinavir sulfate |
Protease inhibitors and antiretroviral |
Improved influx for activity against acquired immune deficiency syndrome (AIDS) |
36 |
|
3. |
Capsaicin |
Neuropeptide releasing agent and analgesic |
Increase skin penetration |
8,49 |
|
4. |
Interferon-α |
Antiviral and anti -neoplastic agent |
Efficient delivery means (because delivery other route is difficult). Controlled release. Overcome stability problem. |
57
|
|
5. |
Norgesterol |
Oral contraceptive |
Improved transdermal flux |
15 |
|
6. |
Tamoxifen |
Selective Estrogen Receptor Modulators (SERM) |
Improved transdermal flux |
16 |
|
7. |
Methotrexate |
Anti-neoplastic and immunosuppressant |
Improved transdermal flux |
54 |
|
8. |
Oestradiol |
Steroidal hormone |
Improved transdermal flux |
53 |
|
9. |
Tetracaine, Lignocain |
Local anaesthetic |
Suitable means for the noninvasive treatment of local pain ondirect topical drug application. |
53, 43 |
|
10. |
Corticosteroids |
Anti-inflammatory agent |
Improved site specificity and overall drug safety. |
20 |
|
11. |
Hydrocortisone |
Anti-inflammatory agent |
Biologically active at dose several times lower than currently used formulation. |
20 |
|
12. |
Triamcinolone Acetonide |
Glucocorticoid |
Used for both local and systemic delivery. |
20 |
|
13. |
Human serum Albumin |
Protein |
Antibody titer is similar or even slightly higher than subcutaneous injection. |
16 |
|
14. |
Stavudine |
Antiretroviral |
Improved the in vitro skin delivery of Stavudine for antiretroviral activity |
36 |
CONCLUSION :
From our study, we can conclude that transfersomes have wider applications with high scopes in future and are nearly as efficient as water in crossing through the barriers of skin. They can be used to enhance the permeability of both high and low molecular weight drugs. Through their ability to deform and reform their shape, they make themselves flexible to pass through tiny pores present in their skin. When compared to that of liposomes, transfersomes are proving to be more efficient in delivering drugs across the barriers. Further research can be extended to formulate drug in transfersomes for treatment of various diseases like cancer especially skin cancer and psoriasis.
ACKNOWLEDGMENT:
This work was supported by the respected Dean and faculties of SRM College of Pharmacy, SRM Institute of science and technology, Kattankullatur.
CONFLICT OF INTEREST:
This article does not contain any conflict of interest.
REFERENCE:
1. Cevc G. Material transport across permeability barriers by means of lipid vesicles In: Lipowsky R, editor. Handbook of physics of biological systems. Amsterdam: Elsevier Science. 1994; Vol. I. Vol. 9 pp : 441–466.
2. Cevc G, Blume G, Schatzlein A, et al. The skin: a pathway for the systemic treatment with patches and lipid-based agent carriers. Adv Drug Delivery Rev. 1996; 18 : 349–378.
3. Cevc G, Schatzlein A, Blume G. Transdermal drug carriers: basic properties, optimization and transfer-efficiency in the case of epi-cutaneously applied peptides. Journal Control Release. 1995; 36 : 3–16.
4. W.F. Lever and G.Schaumburg-Lever. Histopathology of the skin. J.B. Lippincott Company. 1990 ; seventh edition.
5. D. Batisse , R. Bazin, T. Baldeweck, B. Querleux, and J.L. Leveque. Influence of age on the wrinkling capacities of skin. Skin Research and Technology. 2002; (8) : 148-154.
6. El Zaafarany GM , Awad GAS, Holayel SM, Mortada ND. Role of edge activators and surface charge in developing ultra-deformable vesicles with enhanced skin delivery. International Journal Pharm. 2010; 397 : 164-172.
7. Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to transdermal osmotic gradient and hydration force. Biochem Biophys Acta. 1992 ; 1104 : 226-32.
8. Long XY , Luo JB, Li LR, Lin D, Rong HS, Huang WM. Preparation and in vitro evaluations of topically applied capsaicin transfersomes. Zhongguo Zhong Yao Za Zhi. 2006 ; 31 (12) : 981-4.
9. Gregor C. Preparation for the application of agents in minidroplets. US20070042030A1, 2007.
10. Myschik J, Rades T, Hook S. Advances in lipid based subunit vaccine formulations. Curr Immunol Rev. 2009 ; 5 : 42–48.
11. Swarnlata S , Gunjan J, Chanchal DK and Shailendra S. Development of novel herbal cosmetic cream with Curcuma longa extract loaded transfersome for anti-wrinkle effect. African Journal of Pharmacy and Pharmacology. 2011; 5(8) : 1054-62.
12. Jain NK. Advances in Controlled and Novel Drug Delivery. CBS Publishers and Distributers. New Delhi, 2001; First edition : pp.426-451.
13. Modi CD, Bharadia PD. Transfersomes: New Dominants for Transdermal Drug Delivery. Am. J. PharmTech Res. 2012 ; 2 (3): 71-91.
14. Prajapati ST, Patel CG, Patel CN. Transfersomes: A Vesicular Carrier System For Transdermal Drug Delivery. Asian Journal of Biochemical and Pharmaceutical Research. 2011; 2 (1): 507-524.
15. Kombath RV , Minumula SK, Sockalingam A et al. Critical issues related to transfersomes – novel Vesicular system, Acta Sci. Pol. Technol. Aliment. 2012; 11 (1): 67-82.
16. Walve JR , Bakliwal SR, Rane BR, Pawar SP. Transfersomes : A surrogated carrier for transdermal drug delivery system. International Journal of Applied Biology and Pharmaceutical Technology. 2011; 2 (1) : 201-214.
17. Panchagnula R. Transdermal delivery of drugs. Indian Journal of Pharmacology. 1997; 29 : 140-56.
18. Bain KR , Hadgkraft AJ, James WJ and Water KA. R. Prediction of percutaneous penetration Cardiff. STS Publishing. 1993; 3b : 226-34.
19. M. M. Elsayed , O. Y. Abdallah, V. F. Naggar and N. M. Khalafallah. Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. Pharmazie. 2007;62 : 133.
20. Cevc G, Blume G, Schatzlein A: Transfersomes-mediated transepidermal delivery improves the regiospecificity and biological activity of corticosteroids in vivo. J Controlled Release. 1997; 45: 211-216.
21. G. Cevc, D. Grbauer, A. Schatzlein and G. Blume. Biochem. Acta. 1998; 1368: 201.
22. M. Gamal, M. Maghraby, A. C. Williams, B. W. Barry. Journal of Pharmacy &Pharmacology. 1999; 51: 1123.
23. Cevc G, “Isothermal lipid phase”, Transitions Chemistry and Physics of Lipids. 1991; 57: 293-299.
24. Honeywell-Nguyen PL, Bouwstra JA. Vesicles as a tool for transdermal and dermal delivery. Drug Discovery Today: Technologies. 2005; 2(1) : 67-74.
25. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965; 13 : 238–252.
26. Singh H Utreja P, Tiwary A, et al. Elastic liposomal formulation for sustained delivery of colchicine: in vitro characterization and in vivo evaluation of anti-gout activity. Aaps J. 2009 ; 11 : 54–64.
27. Abdallah M. Transferosomes as a transdermal drug delivery system for enhancement the antifungal activity of nyastatin. International Journal of Pharmacy and Pharmaceutical Sciences. 2013; 4(5) : 560-567.
28. Sazoka F, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci. 1978 ; 75 : 4194–4198.
29. Shashank J, Niketkumar P, Mansi KS, et al. Recent advances in lipid-based vesicles and particulate carriers for topical and transdermal application. J Pharm Sci. 2016; 116 (2) : 423 – 445.
30. Kumar A, Adde S, Kamble R, et al. Development and characterization of liposomal drug delivery system for nimesulide. Int J Pharm Pharm Sci. 2010 ; 2 : 87–89.
31. Charcosset C , Juban A, Valour J, et al. Preperation of liposomes at large scale using ethanol injection method: effect of scale up and injection devices. Chem Eng Res Des. 2015; 94 : 508–515.
32. Patel R , Singh SK, Singh S, Sheth NR, Gendle R. Development and Characterization of Curcumin Loaded Transfersome for Transdermal Delivery. J Pharm Sci Res. 2009; 1(4) : 71-80.
33. Maestrelli F, Rodriguez M, Rabasco A, et al. Effect of preparation techniques on the properties of liposomes encapsulating ketoprofen- cyclodextrine complexes aimed for transdermal delivery. Int J Pharm. 2006; 312 : 53–60.
34. Rai K. Transfersomes: self-optimizing carriers for bioactives. PDA J Pharm Sci Technol. 2008 ; 62 : 362–379.
35. Sheo DM , Shweta A, Ram CD, Ghanshyam M, Girish K, Sunil KP. Transfersomes- a Novel Vesicular Carrier for Enhanced Transdermal Delivery of Stavudine: Development, Characterization and Performance Evaluation. J Scientific Speculations and Res. 2010; 1(1) : 30 – 36.
36. Sheo Datta Maurya , Shweta Aggarwal, Vijay Kumar Tilak et al. Enhanced Transdermal delivery of indinavir sulfate via transfersomes. International Journal Of Comprehensive Pharmacy (IJCP). 2010; 1 (06) : 1-7.
37. Gamal M , EI Maghraby M, Williams AC and Barry BW. Skin delivery of oestradiol from deformable and traditional liposomes. Journal of Pharmacy and Pharmacology 1999; 51(10) : 1123-34.
38. Gavali MS , Pacharane SS, Jadhav RK and Kadam JV . Transferosome: A new technique for transdermal drug delivery. International Journal of Research in Pharmacy and Chemistry. 2011; 1(3) : 735-40.
39. Pandey S , Goyani M, Devmurari V, Fakir J. Transferosomes: A Novel Approach for Transdermal Drug Delivery, Der Pharmacia Letter, 2009; 1 (2) : 143-150.
40. Jalon GE , Ygartua P, Santoyo S. Topical application of acyclovir-loaded microparticles: quantification of the drug in porcine skin layers. J. Control Release. 2001; 75: 191-197.
41. Schatzlein A, Cevc G. Skin penetration by phospholipids vesicles, Transfersomes as visualized by means of the Confocal Scanning Laser Microscopy, in characterization, metabolism, and novel biological applications. AOCS Press. 1995 : 191-209.
42. Mahmoud M Omar , Omiya Ali Hasan, and Amani M El Sisi . Preparation and optimization of lidocaine transferosomal gel containing permeation enhancers: a promising approach for enhancement of skin permeation. Int J Nanomedicine. 2019; 14 : 1551–1562.
43. Planas ME , Gonzalez P, Rodriguez L, Sanchez S, Cevc G. Non-invasive percutaneous induction of topical analgesia by a new type of drug carrier, and prolongation of local pain insensitivity by anesthetic liposomes. 1992; 75(4) : 615-621.
44. Shaji J and Lal M. Preparation, optimization and evaluation of transferosomal formulation for enhanced transdermal delivery of a COX-2 inhibitor. Int J Pharm Pharm Sci. 2014 ; 6 : 467-477.
45. Sureewan Duangjit , Praneet Opanasopit, Theerasak Rojanarata, and Tanasait Ngawhirunpat. Characterization and In-Vitro Skin Permeation of Meloxicam-Loaded Liposomes versus Transfersomes. Journal of Drug Delivery Volume 2011; 1-9
46. B. S. Makhmalzadeh , A. Salimi , A. Nazarian and G. Esfahani. Formulation, characterization and in vitro / ex vivo evaluation of trolamine salicylate - loaded transfersomes as transdermal drug delivery carriers. International Journal of Pharmaceutical Sciences and Research. 2018; 9(9) : 3725-3731.
47. Pravin K. Shende , Ravindra L. Bakal, R.S. Gaud, Kiran N. Batheja and Madhugandha S. Kawadiwale. Modulation of serratiopeptidase transdermal patch by lipid-based transfersome. Journal of Adhesion Science and Technology. 2015; volume 29 (23): 2622-2633.
48. Prem N. Gupta, Vivek Mishra, Paramjit Singh et al. Tetanus toxoid‐loaded transfersomes for topical immunization. Journal of Pharmacy and Pharmacology. 2005 ; Volume 57(3) : 295-301.
49. Benson HA. Transfersomes for transdermal drug delivery. Expert Opin. Drug Deliv. 2006; 3 (6) : 727-37.
50. Z. Zhang, X. Wang, X. Chen, Y. Wo, Y. Zhang, and Ewelina Biskup. 5-Fluorouracil-Loaded Transfersome as Theranostics in Dermal Tumor of Hypertrophic Scar Tissue. Journal of Nanomaterials. 2015: 1-9.
51. Lu Y , Hou SX, Zhang LK, Li Y, He JY, Guo DD. Transdermal and lymph targeting transfersomes of vincristine. Yao Xue Xue Bao. 2007; 42(10) :1097-1101
52. Gregor Cevc, Gabriele Blume and Andreas Schatzlein. Transfersomes-mediated trans epidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo . Journal of Controlled Release. 1997; 45(3) : 211-226.
53. Maghraby EI , Williams GM and Barry BW. Skin delivery of oestradiol from lipid vesicles : importance of liposome structure. International Journal of Pharmaceutics. 2000; 204 (1-2) : 159-69.
54. Trotta M Trotta M, Peira E, Carlotti ME and Gallarate M. Deformable liposomes for dermal administration of methotrexate. International Journal of Pharmaceutics. 2004 ; 270 : 119-25.
55. De Marco Almeida , Flavia; Silva, Carolina N.; de Araujo Lopes, Savia Caldeira; Santos, Daniel Moreira; Torres, Fernanda Silva; Cardoso, Felipe Lima; Martinelli, Patricia Massara; da Silva, Elizabeth Ribeiro; de Lima, Maria Elena; Miranda, Lucas A. F.; Oliveira, Monica Cristina . Physicochemical Characterization and Skin Permeation of Cationic Transfersomes Containing the Synthetic Peptide PnPP-19. Current Drug Delivery. 2018;15(7) : 1064-1071(8)
56. Laxmi MV and Zafaruddin MD. Design and characterization of transferosomal gel of repaglinide. Int Res J Pharm 2015 ; 6 : 38-42.
57. Hafer C , Goble R, Deering P, Lehmer A, Breut J. Formulation of interleukin-2 and interferon-alpha containing ultra-deformable carriers for potential transdermal application . Anticancer Res. 1999; 19 (2c) : 1505-7.
58. Mona Qushawy , Ali Nasr, Mohammed Abd-Alhaseeb and Shady Swidan. Design, Optimization and Characterization of a Transfersomal Gel Using Miconazole Nitrate for the Treatment of Candida Skin Infections. Pharmaceutics 2018; 10(1) : 26.
59. Sakshi Sharma Dogra and Simran Chaurasia. Transfersomes: Novel Approach for Intranasal Delivery . EJPMR . 2017 ; 4(3) : 192-203.
Received on 23.08.2019 Modified on 19.09.2019
Accepted on 25.10.2019 © RJPT All right reserved
Research J. Pharm. and Tech 2020; 13(5):2493-2501.
DOI: 10.5958/0974-360X.2020.00445.X