AN OVERVIEW OF ETHOSOME AS ADVANCED Vesicular systems are one ... AN OVERVIEW OF ETHOSOME AS ADVANCED HERBAL DRUG ... The “Somes” are the cell like formulations of novel drug delivery

REVIEW ARTCLE B.Shah et al, IJRRPAS,2(1)., 1-14 ISSN 2249-1236

1 Available on www.ijrrpas.com

1.Department of Pharmacognosy,

L.M. College of Pharmacy,

Navarangpura, Ahmedabad-380013, Gujarat, India.

2. Department of

Pharmacognosy, Faculty of

Pharmacy, Dharmsinh Desai

University, Nadiad-387001,

Gujarat, India.

3. L.J. College of Pharmacy, Ahmedabad, Gujarat, India.

ABSTRACT Ethosomes are the ethanolic phospholipid vesicles which are used mainly for transdermal delivery of

drugs. Ethosomes have higher penetration rate through the skin as compared to liposomes and hence,

these can be used widely in place of liposomes. The increased permeation of ethosomes is probably due

to its ethanolic content. Ethanol increases the cell membrane lipid fluidity which results in increased skin

penetrability of the ethosomes. However, transdermal administration of drugs is generally limited by the

barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal

delivery of active substances. The interest in designing transdermal delivery systems was relaunched after

the discovery of elastic vesicles: transferosomes and liposomes. This article reviews various aspects of

ethosomes including their preparation, characterization, potential advantages and their applications in drug

delivery. Because of their unique structure, ethosomes are able to encapsulate and deliver through the

skin highly lipophilic molecules such as cannabinoids, testosterone and minoxidil, as well as cationic

drugs such as propranolol, trihexyphenydil, cyclosporine A, insulin, salbutamol etc. . Ethosomes provides

a number of important benefits including improving the drug’s efficacy, enhancing patient’s compliance

and comfort and reducing the total costs of treatment.

Keywords: Ethosomes, Preparation, Characterization, Stability.

AN OVERVIEW OF ETHOSOME AS ADVANCED HERBAL DRUG DELIVERY SYSTEM

Dr. Mamta B. Shah*1,

Anar J. Shah2, Rahul Shah

3

International Journal of Research and Reviews in Pharmacy and Applied science

www.ijrrpas.com



1. INTRODUCTION

The “Somes” are the cell like formulations of novel drug delivery system. There are different types of somes like

Liposomes, which encapsulate water and lipid-soluble pharmacologically and cosmetically active components.

Phytosomes are standardized extracts or purified fractions complexed with phospholipids for a better bioavailability

and enhanced activities. Cubosomes are the bicontinuous cubic phases, consisting of two separate, continuous, but

nonintersecting hydrophilic regions divided by a lipid layer that is contorted into a periodic minimal surface with

zero average curvature. Colloidosomes are solid microcapsules formed by the self-assembly of colloidal particles at the

interface of emulsion droplets. Colloidosomes are hollow, elastic shells whose permeability and elasticity can be

precisely controlled. Ethosomes are non-invasive delivery carriers that enable drugs to reach the deep skin layers

and/or the systemic circulation. Ethosomes contain phospholipids, alcohol (ethanol and isopropyl alcohol) in relatively

high concentration and water. Aquasomes are spherical 60300nm particles used for drug and antigen delivery. The

particle core is composed of noncrystalline calcium phosphate or ceramic diamond, and is covered by a polyhydroxyl

oligomeric film. Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids and may exist as

ultrafine vesicular, micellar, or hexagonal aggregates, depending on the chemical structure of the drug–lipid complex.

Niosomes are nonionic surfactant vesicles and, as liposomes, are bilayered structures. etc. [1]

The vesicles have been well known for their important in cellular communication and particle transportation for many

years. Researchers have understood the properties of vesicle structures for use in better drug delivery within their

cavities that would allow tagging the vesicle for cell specificity. Vesicles would also allow to control the release rate

of drug over an extended time, keeping the drug shielded from immune response or other removal systems and

would be able to release just the right amount of drug and keep that concentration constant for longer periods of

time. One of the major advances in vesicle research was the finding a vesicle derivative, known as “Ethosomes”. [2, 3]

Ethosomes are soft, malleable vesicles composed mainly of phospholipids, ethanol (relatively high concentration) and

water. These “soft vesicles” represents novel vesicular carrier for enhanced delivery through the skin. The size of

ethosomes vesicles can be modulated from tens of nanometers to microns.



2. COMPOSITION OF ETHOSOMES:

The ethosomes (Figure 1) are vesicular carrier comprised of hydroalcoholic or hydro/alcoholic/glycolic phospholipid in

which the concentration of alcohols or their combination is relatively high. Typically, ethosomes may contain

phospholipids with various chemical structures like phosphatidylcholine (PC), hydrogenated PC, phosphatidic acid (PA),

soya phospholipids (Phospholipon 90 (PL-90)), phosphatidylserine (PS), phosphatidylethanolamine (PE),

phosphatidylglycerol (PPG), phosphatidylinositol (PI), hydrogenated PC, alcohol (ethanol or isopropyl alcohol), water

and glycol (propylene glycol or transcutol) Such a composition enables delivery of high concentration of active

ingredients through skin. Drug delivery can be modulated by altering alcohol: water or alcohol-polyol: water ratio.

Cholesterol at concentrations ranging between 0.1-1% can also be added to the preparation. In addition, non-ionic

surfactants (PEG-alkyl ethers) can be combined with the phospholipids in these preparations. Cationic lipids like

cocoamide, POE alkyl amines, dodecylamine, cetrimide etc. can be added too. The concentration of alcohol in the final

product may range from 20 to 50%. The concentration of the non-aqueous phase (alcohol and glycol combination)

may range between 22 to 70%. [4] (Table 1)

3. MECHANISM OF DRUG PENETRATION:

Although the exact process of drug delivery by ethosomes remains a matter of speculation, most likely, a combination

of processes contribute to the enhancing effect. The stratum corneum lipid multilayer at physiological temperature are

densely packed and highly conformationally ordered. The high concentration of ethanol makes the ethosomes unique,

as ethanol is known for its disturbance of skin lipid bilayer organization; therefore, when integrated into a vesicle

membrane, it gives that vesicles have the ability to penetrate the stratum corneum. Also because of their high ethanol

concentration, the lipid membrane is packed less tightly than conventional vesicles but has equivalent stability,

allowing a more malleable structure, giving it more freedom and ability to squeeze through small places such as the

openings created in disturbing the stratum corneum lipid. [5]

Ethanol interacts with lipid molecules in the polar hard group region, resulting in a reducting the rigidity of the

stratum corneum lipids, increasing their fluidity. The intercalation of ethanol into the polar head group environment

can result in an increase in the membrane permeability. In addition to the effect of ethanol on stratum corneum

structure, the ethosome itself may interact with the stratum corneum barrier. [6]

The interdigitated, malleable ethosome vesicle can forge paths in the disordered stratum corneum. In the case of

ethosomes encapsulating drugs, the higher positive zeta potential imparted by the drug can improve skin attachment



of the vesicles. While encapsulated drug in classic liposomes remained primarily at the surface of the skin, the

ethosomal system was showed to be highly efficient carrier for enhanced drug delivery through the skin. The efficient

drug deliveries shown together with the long-term stability of ethosomes makes this system a promising candidate for

transdermal delivery of drug.

4.METHODS OF PREPARATION OF ETHOSOMES:

4.1 Hot method:

The drug is dissolved in a mixture of ethanol and propylene glycol and the mixture is added to the phospholipid

dispersion in water at 40ºC. After mixing for five minutes the preparation is sonicated at 4ºC for three cycles of five

minutes, with a rest of five minutes between each cycle, using the Probe Sonicator. The formulation is then

homogenized at 15,000-psi pressure, in three cycles, using a high-pressure homogenizer to get nano-sized ethosomes.

4.2 Cold Method

This is the most common and widely used method for ethosomal preparation. The phospholipids, drug, and other

lipid materials are dissolved in ethanol, in a covered vessel, at room temperature, with vigorous stirring. The mixture

is heated up to 30ºC in a water bath. The water is heated to 30ºC in separate vessel, and added to the above

mixture and then stirred for five minutes in a covered vessel. The vesicle size of the ethosomal formulation can be

decreased if desired, to extend using the sonication or extrusion[7]. Finally the formulation must be properly stored

under refrigeration.[8]

4.3 Classic Mechanical Dispersion Method:

Soya phosphotidylcholine is dissolved in a mixture of chloroform: methanol (3:1) in round bottom flask. The organic

solvents are removed using rotary vacuum evaporator above lipid transition temperature to form of a thin lipid film

on wall of the flask. Finally, traces of solvent mixture are removed from the deposited lipid film by leaving the

contents under vacuum overnight. Hydration is done with different concentration of hydroethanolic mixture containing

drug by rotating the flask at suitable temperature. [9,10]



4.4 Classic Method

The phospholipid and drug are dissolved in ethanol and heated to 30ºC±1ºC in a water bath. Double distilled water

is added in a fine stream to the lipid mixture, with constant stirring at 700 rpm, in a closed vessel. The resulting

vesicle suspension is homogenized by passing through a polycarbonate membrane using a hand extruder for three

cycles.[10]

4. VARIOUS METHODS FOR CHARACTERIZATION OF ETHOSOMES:

Visualization: Visualization of ethosomes can be done using transmission electron microscopy (TEM) and by

scanning electron microscopy (SEM) . [11]

Vesicle size and Zeta potential: Particle size and zeta potential can be determined by dynamic light scattering

(DLS) using a computerized inspection system and photon correlation spectroscopy (PCS). [12]

Entrapment Efficiency: The entrapment efficiency of drug by ethosomes can be measured by the ultracentrifugation

technique. [13]

Transition Temperature: The transition temperature of the vesicular lipid systems can be determined by using

differential scanning calorimetry [14].

Surface Tension Activity Measurement: The surface tension activity of drug in aqueous solution can be measured

by the ring method in a Du Nouy ring tensiometer[15] .

Vesicle Stability: The stability of vesicles can be determined by assessing the size and structure of the vesicles

over time. Mean size is measured by DLS and structure changes are observed by TEM [16].

Drug Content: Drug can be quantified by a modified high performance liquid chromatographic method [17].

Penetration and Permeation Studies: Depth of penetration from ethosomes can be visualized by confocal laser

scanning microscopy (CLSM) [18].

5. ADVANTAGES OF ETHOSOMAL DRUG DELIVERY:

In comparison to other transdermal & dermal delivery systems,

Ethosomes are enhanced permeation of drug through skin for transdermal and dermal delivery.

Ethosomes are platform for the delivery of large and diverse group of drugs (peptides, protein molecules).

Ethosome composition is safe and the components are approved for pharmaceutical and cosmetic use.

Low risk profile- The technology has no large-scale drug development risk since the toxicological profiles of the

ethosomal components are well documented in the scientific literature.



High patient compliance- The ethosomal drug is administrated in semisolid form (gel or cream), producing high

patient compliance. In contrast, iontophoresis and phonophoresis are relatively complicated to use which will affect

patient compliance.

High market attractiveness for products with proprietary technology. Relatively simple to manufacture with no

complicated technical investments required for production of Ethosomes.

The Ethosomal system is passive, non-invasive and is available for immediate commercialization.

Various applications in pharmaceutical, veterinary, cosmetic field. [19]

6. APPLICATION OF ETHOSOMES:

As a drug carrier. (Table 2)

Incosmetics.

The advantage of applying ethosomes in cosmeceuticals is not only to increase the stability of the cosmetic

chemicals and decrease skin irritation from the irritating cosmetic chemicals, but also for transdermal permeation

enhancement, especially in the elastic forms. [20] However, the compositions and sizes of the vesicles are the main

factors to be considered to obtain these advantages of the elastic vesicles for cosmeceutical applications.

Topical administration of many antioxidants is one of the several approaches to diminish oxidative injury in

the skin for cosmetic and cosmeceutical applications. However, antioxidants are usually not stable and can be

degraded by exposing to light. These antioxidants include vitamin E, vitamin C, and flavonoids. Vitamin E is one of

the major exogenous lipophilic antioxidants, which is usually found in tissues.

Its topical application can enhance the skin protection from exogenous oxidants. When vitamin E is added to

cosmetics and many dermatological products, it is found to decrease the production of lipid peroxides in the

epidermis as well as to protect against UV exposure and some destructive chemicals and physical agents. In order

to deliver vitamin E into the deeper layer of SC, Koli et al have formulated 'Anti-oxidant Ethosomes for Topical

Delivery Utilizing the Synergistic Properties of Vitamin A Palmitate, Vitamin E, and Vitamin C,' and the findings

have revealed that the synergistic interaction of Vitamin C in the aqueous core and Vitamin A and E in the lipid

bilayer, provide complete protection from the oxidation of the ethosome formulations. This has suggested that

although elastic and non-elastic liposomes are not beneficial for the delivery of α-tocopherol through the skin, the

entrapment of the vitamin either in elastic or non-elastic liposomes can increase its photo-stability under UVB

irradiation.[21] In a study by Esposito et al., 2004, [22] ethosomes and liposomes of azelaic acid (Anti-keratinizing

http://www.japtr.org/article.asp?issn=2231-4040;year=2010;volume=1;issue=3;spage=274;epage=282;aulast=Verma#ref36

http://www.japtr.org/article.asp?issn=2231-4040;year=2010;volume=1;issue=3;spage=274;epage=282;aulast=Verma#ref38



agent used in the treatment of acne) were prepared as a topical vehicle (gel) and the result demonstrated that

ETHOS 40 could be responsible for a higher azelaic acid, with respect to ETHOS 20 and liposomes. A USA

company, Osmotics Inc., reported new cellulite cream called lipoduction, which used ethosome technology that

penetrated the skin lipid barrier and delivered ingredients directly into the fat cells. Ingredients in lipoduction

improved the appearance of cellulite by up to 80% in less than 60 days.

Pilosebaceous targeting.

Hair follicles and sebaceous glands are increasingly being recognized as potentially significant elements in the

percutaneous drug delivery. Interest in pilosebaceous units has been directed towards their use as depots for

localized therapy, particularly for the treatment of follicle-related disorders such as acne or alopecia. Furthermore,

considerable attention has also been focused on exploiting the follicles as transport shunts for systemic drug

delivery [23]. With the purpose of pilosebaceous targeting, Maiden et al. [24] prepared and evaluated minoxidil

ethosomal formulation. Minoxidil is a lipid-soluble drug used topically on the scalp for the treatment of baldness.

Conventional topical formulation has very poor skin permeation and retention properties. It was found that the

quantity of minoxidil accumulated into mice skin after application of its ethosomal formulation was 2.0, 7.0 and

5.0 fold higher as compared to ethanolic phospholipids dispersion, hydroetanolic solution and ethanolic solution of

drug each containing 0.5% of the drug. These results showed the possibility of using ethosomes for pilosebaceous

targeting of minoxidil to achieve its better clinical efficacy.

Transdermal delivery of hormones.

Oral administration of hormones is associated with problems like high first pass metabolism, low oral

bioavailability and several dose dependent side effects. In addition, along with these side effects oral hormonal

preparations relying highly on patient compliance. The risk of failure of treatment is known to increase with each

pill missed [25].

Touitou et al. [26] compared the skin permeation potential of testosterone ethosomes (Testosome) across

rabbit pinna skin with marketed transdermal patch of testosterone (Testoderm¨ patch, Alza). They observed nearly

30-times higher skin permeation of testosterone from ethosomal formulation as compared to that marketed

formulation. The AUC and Cmax of testosterone significantly improved after application of Testosome as compared

to Testoderm. In vitro and in vivo studies demonstrated that there was an improvement in the skin permeation and

bioavailability of testosterone from ethosomal formulation. This group in their further study designs the



testosterone nonpatch formulation to reduce the area of application [27]. They have found that with ethosomal

testosterone formulation area of application required to produce the effective plasma concentration was 10 times

less than required by commercially gel (AndroGel¨) formulation.

7. STABILITY OF ETHOSOMES:

Stability of the formulations was evaluated in terms of the entrapment capacity and the particle size for a specified

period. Basically, the proper choice of the lipid composition appeared to be an important factor in obtaining stable

ethosomes dispersions with optimum pharmaceutical and therapeutic characteristics. In case of liposomes, upon

storage, many different changes could occur. Liposomes tend to fuse and grow into bigger vesicles and this fusion

and breakage of liposomes on storage pose an important problem of drug leakage from the vesicles. The absence of

electrostatic repulsion is likely to account for the tendency of the neutral liposome to aggregate, but in case of

ethosomes, ethanol causes a modification of the net charge of the system and confers it some degree of steric

stabilization leading to increased stability of the dispersion against agglomeration that may also lead to a decrease in

the mean vesicle size. Increasing the concentration of ethanol from 15 to 45% increases the entrapment efficiency

owing to an increase in the fluidity of the membranes. However, a further increase in the ethanol concentration (>

45%) probably makes the vesicle membrane leakier, thus leading to a decrease in entrapment efficiency. Therefore, it

causes destabilization of the ethosomes. The lipid portion of the ethosomes is derived from natural and / or synthetic

phospholipid sources. Phospholipids containing unsaturated fatty acids are known to undergo oxidative reactions. The

reaction products can cause permeability changes in the ethosomes bilayers. Oxidative degradation of the lipids in

general can be minimized by protecting the lipid preparation from light, by adding antioxidants such as α-tocopherol.

Furthermore, hydrolysis of lipids leads to the formation of lyso-PC. The presence of lyso-PC enhances the permeability

of ethosomes, and thus, it is essential to keep its level to a minimum in a given preparation.[28,29]

8. FUTURE PROSPECTS

Introduction of ethosomes has initiated a new area in vesicular research for transdermal drug delivery. Different

reports show a promising future of ethosomes in making transdermal delivery of various agents more effective.

Further, research in this area will allow better control over drug release in vivo, allowing physician to make the

therapy more effective. Ethosomes offers a good opportunity for the non-invasive delivery of small, medium and large

sized drug molecules. The results of the first clinical study of acyclovir-ethosomal formulation support this conclusion.

Multiliter quantities of ethosomal formulation can be prepared very easily. It, therefore, should be not before long



that the corresponding drug formulation would have found their way into clinics to be tested for widespread usage.

Thus, it can be a logical conclusion that ethosomal formulations possess promising future in effective

dermal/transdermal delivery of bioactive agents.

Figure 1: Composition of Ethosomes in Vesicular Structure.

Figure 2: Mechanism of Ethosome-Vesicular Delivery System.



Class Example Uses

Phospholipid

Soya phosphatidyl

choline, Egg

phosphatidyl choline,

Dipalmityl

phosphatidyl choline,

Distearyl phosphatidyl

choline.

Vesicles forming

component.

Polyglycol Propylene glycol

Transcutol RTM

As a skin penetration

enhancer.

Alcohol Ethanol

Isopropyl alcohol

For providing the

softness for vesicle

membrane, As a

penetration enhancer.

Cholesterol Cholesterol

For providing the

stability to vesicle

membrane.

Dye

Rhodamine-123

Rhodamine red

Fluorescene

Isothiocynate (FITC)

6- Carboxy

fluorescence

For characterization

study.

Vehicle Carbopol Ð934 As a gel former.

Table 1: Different Additives Employed In Formulation of Ethosomes



Drugs Results

NSAIDS

(Diclofenac)

Selective delivery of drug to desired side for prolong

period of time.

Acyclovir

Increase skin permeation.

Improved in biological activity two to three times.

Improved in Pharmacodynamic profile.

Insulin Significant decrease in blood glucose level.

Provide control release.

Trihexyphenidyl

hydrochloride

Improved transdermal flux.

Provide controlled release.

Improved patient compliance.

Biologically active at dose several times lower than the

currently used formulation.

DNA Better expression of genes.

Selective targeting to dermal cells.

Antibiotic

Cannabidol

Erythromycin

Improved skin deposition.

Improved biological activity.

Prolonging drug action.

Bacitracin

Improved dermal deposition.

Improved intracellular delivery.

Increased bioavailability.

Anti-HIV agents

Zidovudine

Lamivudine

Improved transdermal flux.

Improved in biological activity two to three times.

Prolonging drug action.

Reduced drug toxicity.

Affected the normal histology of skin.

Azelaic acid Prolong drug release

Ammonium

glycyrrhizinate

Improved dermal deposition exhibiting sustained

release

Improved biological anti-inflammatory activity

Table 2: Application of Ethosomes as a Drug Carrier



9. CONCLUSION

Ethosomal carrier opens new challenges and opportunities for the development of novel improved therapies.

Ethosomes are soft, malleable vesicles and potential carrier for transportation of drugs. Ethosomes are characterized

by simplicity in their preparation, safety and efficacy and can be tailored for enhanced skin permeation of active

drugs. [30] Ethosomes have been found to be much more efficient at delivering drug to the skin, than either

liposomes or hydroalcoholic solution.It can be easily concluded that ethosomes can provide better skin permeation

than liposomes. The main limiting factor of transdermal drug delivery system i.e. epidermal barrier can be overcome

by ethosomes to significant extent. Application of ethosomes provides the advantages such as improved permeation

through skin and targeting to deeper skin layers for various skin diseases.

REFERENCES:

[1] Reference: Vinod KR et al., A Review On Genesis And Characterization Of Phytosomes, International Journal of

Pharmaceutical Sciences Review and Research, September – October 2010; Volume 4, Issue 3, Article 013,69-72.

[2] Jain S, Bhandra D, Jain S and Jain N K., Transfersomes, A Novel carrier for effective transdermal drug delivery

controlled and novel drug delivery, 1st Edition, CBS Publishers and Distributors, New Delhi, 1997: 426-451.

[3] Touitou E, Godin B and Weirs C., Enhanced Delivery into and across the skin by Ethosomal carries, Drug Dev.

Research, 2000, 50, 406-415.

[4] P. M. Mujeeb, Rahman H.H. and Vimal Mathew, ETHOSOMES - A NOVEL DRUG DELIVERY SYSTEM- , National College

of Pharmacy, Manassery, Calicuta

[5] Tauitou E et al., Ethosomes-novel vesicular carriers for enhanced delivery: characterization and skin penetration

properties, J Con Release, 2000, 65, 403-413.

[6] Jain S, Bhandra D, Jain S and Jain N K. Transfersomes-A Novel carrier for effective transdermal drug delivery

controlled and novel drug delivery 1st Edition, CBS Publishers and Distributors,New Delhi,1997,426-451.

[7] Verma D.D. and Fahr, A Synergistic penetration of ethanol and phospholipids on the topical delivery of cyclosporine A, J.

Control Release, 2004, 97, 55-66.

[8] Touitou E, Composition of applying active substance to or through the skin, US patent, 1998, 5,540,934.

[9] Dubey V, Mishra D, Jain NK, Melatonin loaded ethanolic liposomes: Physicochemical characterization and enhanced

transdermal delivery, Eur J Pharm Biopharm, 2007, 67, 398-405.

[10] Jain S, Tiwary AK, Sapra B, Jain N, Formulation and evaluation of ethosomes for



transdermal delivery of lamivudine, AAPS Pharm Sci Tech, 2007,8,1-9.

[11] Touitou E.; Preparation of liposomes and size determination, In:Liposomes A Practical Approach, New RRC (Ed.),

Oxford University Press, Oxford, 1990:36-39.

[12] Guo J, Ping Q, Sun G, and Jiao C, Lecithin vesicular carriers for transdermal delivery of cyclosporine A, Int. J.

Pharm., 2000, 194(2), 201-207.

[13] Maghraby GMM, Williams AC, and Barry BW, Oestradiol skin delivery from

ultradeformable liposomes: refinement of surfactant concentration, Int. J. Pharm., 2000, 196(1), 63-74.

[14] Fry DW, White JC, and Goldman ID, Rapid secretion of low molecular weight solutes from liposomes without

dilution, Anal. Biochem.,1978, 90, 809-815.

[15] Cevc G, Schatzlein A, and Blume G, Transdermal drug carriers: Basic properties,

optimization and transfer efficiency in case of epicutaneously applied peptides, J. Control.

Release, 1995, 36, 3-16.

[16] Vanden Berge BAI, Swartzendruber VAB, and Geest J, Development of an optimal protocol for the ultrastructural

examination of skin by transmission electron microscopy, J. Microsc.,1997, 187(2), 125-133.

[17] Dayan N, and Touitou E, Carrier for skin delivery of trihexyphenidyl HCl: Ethosomes vs liposomes.

Biomaterials,2002, 21, 1879-1885.

[18] Toll R, Jacobi U, Richter H, Lademann J, Schaefer H, and Blume U, Penetration profile of microspheres in follicular

targeting of terminal hair follicles, J. Invest. Dermatol., 2004, 123, 168-176.

[19]Patel S, Ethosomes: A promising tool for transdermal delivery of drug, Pharma Info.Net, 2007,5(3).

[20] Manosrai A, Jantrawut P, Khositsuntiwong N, Manosroi W, Manosroi J. Novel Elastic Nanovesicles for

Cosmeceutical and Pharmaceutical Applications, Chiang Mai J Sci 2009, 36, 168-78.

[21] Koli JR, Lin S., Development of anti oxidant ethosomes for topical delivery utilizing the synergistic properties of Vit

A palmitate, Vit E and Vit C., AAPS Pharm Sci Tec, 2009,11,1-8.

[22] Esposito E, Menegatti E, Cortesi R. Ethosomes and liposomes as topical vehicles for azeliac acid: A preformulation

study, J Cosmet Sci, 2004, 55,253-64.

[23] Lauer A.C. et al., Adv. Drug Deliv. Rev., 1996, 18, 311-324.

[24] Meidan, V.M.; Alhaique, F.; Touitou, E., Acta Technologiae et Legis Medicament. ,1998, 9(1),1-6.

[25] Johnsen, S.G. Bennett, E.P.; Jensen, V.G., Lancet, 1974, 2,1473Ð1475

[26] Touitou E.; Dayan, N.; Bergelson, L.; Godin, B.; Eliaz, M., J. Control. Release, 2000,65,403-418.



[27] Touitou, E., Expert Opin. Biol. Ther., 2002, 2,723-33.

[28] Rao LS., Liposome technology, Preparation of liposomes on the industrial scale: Problems and perspectives. In:

Gregoriadis G, Vol. 1. Florida: CRC Press; 1984.

[29] Anonymous, Preparation of liposomes, Liposomes-a practical Approach, New RRC, Oxford: Oxford University Press;

1990.

[30]Patel S, Ethosomes: A promising tool for transdermal deliveryof drug, Pharma Info.Net, 2007, 5(3)

Documents

AN OVERVIEW OF ETHOSOME AS ADVANCED Vesicular systems are one ... AN OVERVIEW OF ETHOSOME AS ADVANCED HERBAL DRUG ... The “Somes” are the cell like formulations of novel drug delivery