2).pdf · review article ravi b patel et.al / ijipsr / 2 (4), ... vesicular system is ... ethosomal...

REVIEW ARTICLE Ravi B Patel et.al / IJIPSR / 2 (4), 2014, 941-961

Department of Pharmaceutics ISSN (online): 2347-2154

Available online: www.ijipsr.com April Issue 941

ETHOSOME: AN EMERGING TARGETED DRUG DELIVERYSYSTEM A REVIEW

1Ravi B Patel*, 2Tejas B Patel, 3B. N. Suhagia, 4Mehul N Patel, 5Mayur Patel, 6Parth Patel

Faculty of Pharmacy, Dharmsinh Desai University, Nadiad, Gujarat-387001, INDIA

Corresponding Author

Mr. Ravi B Patel

Faculty of Pharmacy,

Dharmsinh Desai University,

Nadiad-387001, Gujarat, INDIA.

E-Mail: [email protected]

Contact No: +91-9033592048.

International Journal of InnovativePharmaceutical Sciences and Research

www.ijipsr.com

Abstract:

Now-a-days we better known vesicles have importance in cellular communication. Vesicular system isone of the most controversial methods for transdermal delivery of active substances in, that ethosomesare the ethanolic phospholipids vesicles which are used mainly for transdermal delivery of drugs.Ethosomes have higher penetration rate through skin due to its ethanolic content, these carriers opennew challenges and opportunities for the development of novel improved invasive delivery carriers thatenable drugs to reach the deep skin layers and/or the systemic circulation. It is interesting andpioneering vesicular systems that have appeared in the field of pharmaceutical technology and drugdelivery in recent year. Ethosomal drug delivery system is a new state of the art technique and easier toprepare in addition to safety and efficacy. Ethosomes have become an area of research interest, becauseof its enhanced skin permeation, improved drug delivery, increased drug entrapment efficiency etc. Thepurpose of writing this review on ethosomes drug delivery was to compile the focus on the variousaspects of ethosomes including their mechanism of penetration, preparation, advantages,characterization, composition, application and marketed product of ethosomes.

Key Words: Ethosomes, Transdermal drug delivery, Vesicle, Topical delivery, Skin.

Key words:




INTRODUCTION

Skin is the major target for topical and transdermal preparations. For transdermal delivery of

drugs, stratum corneum is the main barrier for permeation of drug. Transdermal delivery is

important because it is a non-invasive procedure for drug delivery. Further, problem of drug

degradation by digestive enzymes after oral administration and discomfort associated with

parenteral drug administration can be avoided [1]. It is the most preferred route for systemic

delivery of drugs to paediatric, geriatric and patients having dysphasia. Hence, transdermal

dosage forms being the most patient compliant mode of drug delivery. Despite the many

advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum

corneum [2, 3, 4].

One simple and convenient approach is application of drugs in formulation with elastic vesicles

or skin enhancers. In that vesicular system is one of the most controversial methods for

transdermal delivery of active substances. In that ethosome are the ethanolic phospholipids

vesicles which are used mainly for transdermal delivery of drugs. These carriers open new

challenges and opportunities for the development of novel improved invasive delivery carriers

that enable drugs to reach the deep skin layers and/or the systemic circulation. They are

interesting and pioneering vesicular systems that have appeared in the field of pharmaceutical

technology and drug delivery in recent years [5-10].

ETHOSOMES

Ethosome are soft, malleable lipid vesicles composed mainly of phospholipids, alcohol (ethanol

or isopropyl alcohol) in relatively high concentration (20-45%) and water. Ethosomes were first

developed by Touitou and her colleagues in 1997.

The ethanol in ethosomes causes disturbance of skin lipid bilayer organization, hence when

incorporated into a vesicle membrane, it enhances the vesicle’s 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. The size range of ethosomes may

vary from tens of nanometers to microns (μ) [12-16].

Figure 1: Proposed diagram of ethosome vesicle

ETHOSOMES COMPOSITION

Ethosomes are vesicular carrier comprise of hydro alcoholic or hydro/alcoholic/glycolic

phospholipid in which the concentration of alcohols or their combination is relatively high

Ethosomal drug delivery can be modulated by altering alcohol: water or alcohol:polyol: water

ratio, Ethosomes may contain phospholipids with various chemical structures like

phosphatidylcholine (PC), hydrogenated PC, phosphatidic acid (PA), phosphatidylserine (PS),

phosphatidylethanolamine (PE), phosphatidylglycerol (PPG), phosphatidylinositol (PI),

hydrogenated PC, alcohol (ethanol or isopropyl alcohol), water and propylene glycol (or other

glycols). Some preferred phospholipids are soya phospholipids such as Phospholipon 90. It is

usually employed in a range of 0.5-10% w/w. Cholesterol at concentrations ranging between 0.1-

1% can also be added to the preparation. Examples of alcohols, which can be used, include

ethanol and isopropyl alcohol. Among glycols, propylene glycol and Transcutol are generally




used [11]. 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%. [17-22]. The various type of additive used in the ethosomes preparations are represented

in Table1.

MATERIALS

Table 1: Materials used in the preparation of ethosomes.

ADVANTAGE OF ETHOSOMES:

1. Enhanced permeation of drug molecules to and through the skin to the systemic

circulation

2. Contrary to deformation liposomes, ethosomes improve skin delivery of drugs both under

occlusive and non-occlusive conditions.

3. Ethosomes composition is safe and the components are approved for pharmaceuticals and

cosmetic use.

Sr. No Class Example Uses

1. Phospholipid

Soya phosphatidyl cholineEgg phosphatidyl choline

Dipalmityl phosphatidyl cholineDistearyl phosphatidyl choline

Vesicles forming component

2. PolyglycolPropylene glycolTranscutol RTM

As a skin penetration enhancer

3. AlcoholEthanol

Isopropyl alcohol

For providing the softness forvesicle membrane As apenetration enhancer

4. Cholesterol Cholesterol Membrane Stabilizing agent5. Vehicle Carpool D934 As a gel former

6. Dyes

Rhodamine-123Rhodamine red

Fluorescene Isothiocynate (FITC)6- Carboxy fluorescence

For characterization study




4. Better patient compliance.

5. Better stability and solubility of many drugs as compared to conventional vesicles.

6. Various applications in pharmaceutical, veterinary and cosmetic field.

7. Relatively smaller size as compared to conventional vesicles.

8. Ease of industrial scale-up: Multiliter quantities of ethosomal formulation can be

prepared easily; do not require any sophisticated or specially designed equipments.

9. Deliver molecules with different physicochemical properties, hydrophilic and lipophilic

molecules.

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

protein molecules) [23,25,28].

DISADVANTAGES OF ETHOSOMES:

1. Drugs that require high blood levels cannot be administered – limited only to potent

molecules, those requiring a daily dose of 10mg or less.

2. Ethosomal administration is not a means to achieve rapid bolus type drug input, rather it

is usually designed to offer slow, sustained drug delivery.

3. Adequate solubility of the drug in both lipophilic and aqueous environments to reach

dermal microcirculation and gain access to the systemic circulation.

4. The molecular size of the drug should be reasonable that it should be absorbed

percutaneous.

5. Adhesive may not adhere well to all types of skin. Uncomfortable to wear.

6. May not be economical. Poor yield

7. Skin irritation or dermatitis due to excipients and enhancers of drug delivery systems.

8. In case if shell locking is ineffective then the ethosomes may coalescence and fall apart

on transfer into water.




9. Loss of product during transfer from organic to water media[24,26,27].

MECHANISM OF DRUG PENETRATION VIA ETHOSOMES:

The main advantage of ethosomes over liposomes is the increase permeation of the drug. The

mechanism of the drug absorption from ethosomes is not clear.

The drug absorption probably occurs in following two phases

1. Ethanol effect

2. Ethosomes effect

1. Ethanol effect:

Ethanol acts as a penetration enhancer through the skin. The mechanism of its penetration

enhancing effect is well known Ethanol penetrates into intercellular lipids and increases the

fluidity of cell membrane lipids and decrease the density of lipid multilayer of cell membrane.

2. Ethosomes effect:

Increased cell membrane lipid fluidity caused by the ethanol of ethosomes results increased skin

permeability. So the ethosomes permeates very easily inside the deep skin layers, where it got

fused with skin lipids and releases the drugs into deep layer of skin [29-33].

Figure 2:Drug penetration through ethosomes.




PREPARATION OF ETHOSOMES:

Mainly two type of Method used for Preparation of Ethosome [19,23]

1. Cold Method

2. Hot Method

Cold Method

Figure 3: Cold Process for preparation of Ethosomes




Hot Method

Figure 4: Hot Process for Preparation of Ethosomes

Mechanical dispersion method

Soya phosphatidylcholine is dissolved in a mixture of chloroform: methanol in round bottom

flask. The organic solvents are removed using rotary vacuum evaporator above lipid transition

temperature to form a thin lipid film on wall of the RBF. 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 RBF at suitable temperature [35].

Classic method

The phospholipid and drug are dissolved in ethanol and heated to 30°C±1°C 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 [36].




CHARACTERIZATION OF ETHOSOMES [37,38,48]

Table 2: Characterization Methods for Evaluation of Ethosomes

Sr.No Equipment Parameter

1.Scanning electron microscopy (SEM),

Transmission electron microscopy (TEM)Vesicle shape and surface morphology

2. Dynamic light scattering technique Vesicle size

3. Ultracentrifugation Drug Entrapment efficiency

4. Modified Franz diffusion cells In-vitro Drug release study

5. Zeta Sizer Zeta Potential

6. Differential scanning Calorimetric Differential scanning Calorimetric

7. Sonicator or Mechanical stirrer Controlled vesicle size

8. Double beam UV Visible Spectrometer Drug Content measurement

Elasticity Measurement

Extrusion Method

The elasticity of ethosome vesicle membrane was determined by extrusion method. The

ethosomal formulations were extruded through filter membrane (pore diameter 50 nm), using a

stainless steel filter holder having 25-mm diameter, by applying a pressure of 2.5bar. The

quantity of vesicle suspension, extruded in 5 minutes was measured. Vesicle shape (by TEM)

and size (by DLS) were monitored before and after filtration. The elasticity of vesicle membrane

was calculated by using the following formula [43,45].




Where, E is elasticity of vesicle membrane; J is the amount of suspension extruded in 5 minutes; rv is

vesicle size (after extrusion); and rp is pore size of the barrier.

APPLICATIONS OF ETHOSOMES

1. PILOSEBACEOUS TARGETING:

For the treatment of follicle related disorders such as acne or alopecia.Pilosebaceous units

have been use for localized therapy Ethosomal formulation of minoxidil a lipid soluble

drug used for baldness accumulate into nude mice skin two to seven fold higher and thus

can be used for Pilosebaceous targeting for better clinical efficacy [39,46].

2. TRANSDERMAL DELIVERY:

Since ethosomes enhance permeability of drug through stratumcorneum barrier, it can be

use for administration of drugs having poor skin permeation, loworal bioavailability, first

pass metabolism and dose dependent side effect. Touitou et alreported that the skin

permeation of testosterone from ethosomal formulation is nearly 30 times higher than the

marketed transdermal patch of testosterone [8, 39, 41].

3. TOPICAL DELIVERY OF DNA:

Another important application of ethosomes is their use for topical delivery of DNA

molecules. Touitou et al demonstrated that better intracellular up take of DNA, better

delivery and expression of genes in skin cells can be achieved by ethosomal formulation

[18]. Hence was concluded that ethosomes can be used carrier for gene therapy application

that require transient expression of genes [42,44,49].

4. DELIVERY OF ANTI-ARTHRITIS DRUG:

Anti-arthritis drug is associated with problems like low bioavailability, GIT degradation,

High first pass metabolism etc. To overcome above problems ethosomal formulation of

anti-arthritis drugs can be used as it significantly increase skin permeation [39,42].




5. DELIVERY OF ANTIBIOTICS:

Ethosomes formulation of antibiotics could be highly efficient and overcome the

problems associated with conventional oral and topical therapy of antibiotic since they

penetrate rapidly into deeper layer of skin and suppress infection at their route [39, 40,

47].

6. DELIVERY OF HIV DRUGS:

An effective antiretroviral therapy is required on a long term basis and is associated with

strong side effects [7]. Adequate zero order delivery of a potent antiviral agent is required

to maintain expected anti – AIDS effect., Conventional topical Ethosomes formulation of

acyclovir show high permeation and therapeutic efficiency with shorter healing time and

higher percentage of abortive lesions to overcome the convential topical preparation

acyclovir an topically used antiviral drug for treatment of herpes labials show low

therapeutic efficiency due to poor permeation through skin as replication of virus take

places at the basal dermis [30,35,46[.

7. DELIVERY OF PROBLEMATIC DRUG MOLECULES:

Oral delivery of large biogenic molecules such as peptides or proteins and insulin is

difficult because they are completely degraded in the GIT tract hence transdermal

delivery is a better alternative. But conventional transdermal formulation of biogenic

molecules such as peptides or protein and insulin has poor permeation. Formulating these

above molecules into ethosomes significantly increase permeation and therapeutic

efficacy [48,50].

8. TRANSDERMAL DELIVERY OF HORMONES:

Oral delivery of hormones produce the problems like high first pass metabolism, low oral

bioavailability and several dose dependent side effects, and increased risk of failure of




treatment if the pill is missed [44,45,49]. The skin permeation potential of testosterone

ethosomes a cross rabbit pinna skin with marketed transdermal patch of testosterone

compared and it was observed nearly 30 times higher skin permeation of testosterone

from ethosomal formulation as compared to that of marketed formulation of testosterone.

Both invitro and in vivo studies demonstrated improved skin permeation and

bioavailability of testosterone from ethosomal formulation.

9. DELIVERY OF ANTI-PARKINSONISM AGENT:

Dayan and Touitou (2002) prepared ethosomal formulation of psychoactive drug

trihexyphenidyl HCl (THP) used in treatment of parkinson disease and compared its

delivery with that from classical liposomal formulation. THP ethosomal formulation

when visualized under TEM and SEM, found to consists of small phospholipid vesicles.

The value of transdermal flux of THP through nude mouse skin from ethosomes was 4.5-

times higher than that from liposome, phosphate buffer and hydroethanolic solution

respectively. At the end of 18 h, quantity of drug remaining in skin was significantly

higher after application of ethosomes as compared to that of application of liposome or

hydroethanolic solution. The results showed the better skin permeation potential of

trihexylphenidyl hydrochloride (THP) ethosomal formulation and its use for better

management of Parkinson disease [49, 53, 54].

10. TRANSCELLULAR DELIVERY:

Touitou et al. in their study demonstrated better intracellular uptake of bacitracin, DNA

and erythromycin using CLSM and FACS techniques in different cell lines. Better

cellular uptake of anti-HIV drug zidovudine and lamivudine in MT-2 cell line from

ethosomes as compared to the marketed formulation suggested ethosomes to be an

attractive clinical alternative for anti-HIV therapy [48,26].




11. DELIVERY OF ANTI-VIRAL DRUGS:

Ethosomal formulation of zidovudine have been developed to increase the transdermal

flux, prolong the release to overcome the problem associated with oral administration of

zidovudine is associated with strong side effects (Jain et al 2004). Acyclovir ethosomal

formulation has been formulated for dermal delivery (Horwitz et al 1999). They have

clinically evaluated its performance in a double blind, randomized study with marketed

formulation of acyclovir(Zovirax, Glaxo-Wellcome) in terms of time to crust formation,

time to loss of crust and proportions of lesions not progressive beyond the popular stage

(abortive lesions). Significant improvement in all evaluated clinical parameters was

observed when disorder was treated with ethosomal formulation in comparison to

marketed formulation. The average time to crusting of lesions was 1.6 vs 4.3 days in the

parallel arm and 1.8 vs 3.5 days in the crossover arm (P<0.025) for ethosomal acyclovir and

zovirax, respectively. Hence, shorter healing time and higher percentage of abortive

lesions were observed when acyclovir was loaded into ethosomes [25, 50, 51].

12. ETHOSOMES USED FOR COSMETICS:

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

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

transdermal permeation enhancement, especially in the elastic forms. Topical

administration of many antioxidants is one of the several approaches to diminish

oxidative injury in the skin for cosmetic and cosmeceutical applications. A USA

company, Osmotic Inc., reported new cellulite cream called lipoduction prepared by

using ethosome technology that penetrated the skin lipid barrier and delivered ingredients

directly into the fat cells [52,29].




Table 3: Marketed products based on ethosomal drug delivery system

CONCLUSION

By this above study it shows that ethosomes can perfectly be used for transdermal delivery as

carrier system. The main rate limiting factor of transdermal drug delivery system in human skin

is stratum corneum layer. Ethosomal carrier opens new challenges and opportunities for the

development of novel improved therapies for Topical and Transdermal route is promising

alternative to drug de-livery for systemic effect. Ethanol is known to have permeation

enhancement property. However, the permeation enhancement from ethosomes is much greater

Name of product Uses Manufacturer

Nanominox

First minoxidil containing product, which uses

ethosomes. Contains 4% Minoxidil, well-known hair

growth promoter,

Sinere, Germany

Decorin cream

Anti-aging cream, treating, repairing, and delaying the

visible aging signs of the skin including wrinkle lines,

age spots, loss of elasticity, and Hyper pigmentation

Genome Cosmetics,

Pennsylvania,

US

Cellutight EF

Topical cellulite cream, contains a powerful

combination of ingredients to increase metabolism and

break down fat,

Hampden Health,

USA

Noicellex Topical anti-cellulite creamNovel Therapeutic

Technologies, Israel

Skin genuity Powerful cellulite buster, reduces orange peelPhysonics,

Nottingham, UK

Supravir cream For the treatment of herpes virus, Trima, Israel




than it would be expected from ethanol alone. Ethosomes provides the easy and fast delivery of

hydrophilic and impermeable drugs through the skin. Ethosomes can be administered in the form

of many dosage forms like cream, patch, ointment, paste etc.

FUTURE PROSPECTS

Invention of ethosomes has started a new area in vesicular research for transdermal drug

delivery. Further, research in this area will allow better control over drug release in vivo,

allowing physician to make the therapy more effective. Ethosomes provide 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. Multilayer

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.

In recent years, the transdermal route of drug delivery has evolved considerably and it now

competes with oral treatment. The market value for Transdermal delivery was $12.7 billion in

2005, and is expected to increase to $21.5 billion in the year 2010 and $31.5 billion in the year

2015 – suggesting a significant growth potential over the next 10 years 13.

REFERENCES

1. Rakesh R, Anoop kr. Ethosomes for transdermal and topical drug delivery.International

Journal of Pharmacy and Pharmaceutical Sciences,2012;24

2. Pratima N, Shailee T, Ethosomes: A Novel Tool for Transdermal Drug Delivery

International Journal of Research in Pharmacy and Science,2012;1-20




3. Tarun P, Soniya, Roopesh S, Vishal S, Gaurav S, Ethosomes: A Recent Vesicle Of

Transdermal Drug Delivery System,International Journal of Research and Development

in Pharmacy and Life Sciences.2013;285-292

4. Pavan Kumar K,Radhika P.R,Sivakumar.T,Ethosomes-A Priority in Transdermal Drug

DeliveryInternational Journal of Advances in Pharmaceutical Sciences 2010; 111-121

5. Prasanthi D and Lakshmi PK,Statistically optimised ethosomes for transdermal delivery

of tolterodine tartrate, Pak. J. Pharm. Sci, November 2013,1117-1122.

6. Lalit Kumar .T, Saurabh Kumar, Shambhu Sharan.M and Mohan Lal.K, Ethosomes:

Delivery System. Bulletin of Pharmaceutical Research 2013;3(1):6-13

7. Jarivis B, Faulds D. Lamivudine: a review of its therapeutic potential in chronic hepatits

B. Drugs, 1999; 58(1): 101 – 141.

8. Touitou E. Drug delivery across skin. Expert Opinion on Biological Therapy, 2002; 2:

723 – 733.

9. Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosome for skin delivery of

ammonium glycyrrhizinate: In vitro percutaneous permeation through human skin and in

vivo anti-inflammatory activity on human volunteers. J Cont Rel 2005; 106:99-110.

10. Jun-Bo T, Zhuang-Qun Y, Xi-Jing H, Ying X, Yong S, Zhe X, Tao C. Effect of

ethosomal minoxidil on dermal delivery and hair cycle of C57BL/6 mice. J Dermatol Sci

2007; 45:135-137.

11. Rong H, Da-xiang C, Feng G. Preparation of fluorescence ethosomes based on quantum

dots and their skin scar penetration properties. Mater Lett 2009; 63:1662-1664.

12. L´opez-Pinto JM, Gonz´alez-Rodr´ýguez ML, Rabasco AM. Effect of cholesterol and

ethanol on dermal delivery from DPPC liposomes. Int J Pharm 2005; 298:1-12.




13. Ming C, Xiangli L, Alfred F. Skin penetration and deposition of carboxyfluorescein and

temoporfin from different lipid vesicular systems: In vitro study with finite and infinite

dosage application. Int J Pharm 2011; 408:223-234.

14. Jain S, Tiwary AK, Sapra B, Jain NK. Formulation and evaluation of ethosomes for

transdermal delivery of lamivudine. AAPS Pharma Sci Tech 2007; 12:E1-E9.

15. Vijayakumar MR, Sathali AHA, Arun K. Formulation and evaluation of diclofenac

potassium ethosomes. Int J Pharm Pharm Sci 2010; 2:82-86.

16. Touitou, E. Composition of applying active substance to or through the skin, US patent,

1996; 5:716,638.

17. Touitou E, Composition of applying active substance to or through the skin. US Patent:

5540934, 1998.

18. Touitou E. Composition and methods for intracellular delivery, 2002; PCT/IL02/00516.

19. Elsayed M M, Abdallah O Y, Naggar V F, Khalafallah N M. Biomaterials Deformable

liposomes andethosomes as carriers for skin delivery of ketotifen. Pharmazie. 2007;62 :

133 – 137.

20. Sanjay Patel, Ethosomes: A promising tool for transdermal delivery of drug,

pharmainfo.net: Accessed on 23 dec 2012.

21. Laib S, Routh A F. Fabrication of colloidosomes at low temperature for the encapsulation

ofthermally sensitive compounds. J. Colloid & Interface Sci. 2008;317 : 121-129.

22. Swarnlata S, Rahul R, Chanchal D.K, Shailendra S. Colloidosomes an advanced vesicular

system in drug delivery. Asian J.Sci. Research 2011;4(1) : 1 – 15.

23. Akiladevi, Sachinandan BasakEthosomes- A Non-invasive approach for Transdermal

Drug Delivery- D , International Journal of Current Pharmaceutical Research Vol-2,issue

4, 2010




24. Gangwar S, Singh S, Garg G, “Ethosomes: A novel tool for drug delivery through the

skin”, Journal of Pharmacy Research 2010, 3 (4), 688-691

25. Jain S, Umamaheshwari R.B, Bhadra D, Jain N.K, Ethosomes: a novel vesicular carrier

for

enhanced transdermal delivery of an anti-HIV agent. Ind. J. Pharm. Sci. 2004;66 : 72-81.

26. Verma D D, Fahr A. Synergistic penetration effect of ethanol and phospholipids on the

topicaldelivery of Cyclosporin. J. Cont.Release 2004;97: 55-66.

27. Berge V, Swartzendruber V.B, Geest J. Development of an optimal protocol for the

ultrastructural examination of skin by transmission electron microscopy. J. Microscopy

1997; 187(2): 125-133.

28. Toll R, Jacobi U, Richter H, Lademann J, Schaefer H, Blume U. Penetration profile of

microspheres in follicular targeting of terminal hair follicles. J. Investigative

Dermatology 2004; 123: 168-176.

29. Lopez-Pinto J.M, Gonzalez-Rodriguez M.L, Rabasco A.M. Effect of cholesterol and

ethanol on dermal delivery from DPPC liposomes. Int. J. Pharma. 2005;298 :1-12.

30. Maghraby G.M, Williams A.C, Barry B.W. Oestradiol skin delivery from

ultradeformableliposomes: refinement of surfactant concentration. Int. J. Pharma. 2000:

63-74.

31. Fry D W, White J.C, Goldman I.D. Rapid secretion of low molecular weight solutes

fromliposomes without dilution. Analytical Biochemistry 1978;90: 809- 815.

32. New R C. Preparation of liposomes and size determination, In:Liposomes A Practical

Approach, New RRC (Ed.), Oxford University Press, Oxford. 1990; 36-3.




33. Cevc G, Schatzlein A, Blume G. Transdermal drug carriers: Basic properties,optimization

and transfer efficiency in case of epicutaneously applied peptides. J. Cont. Release

1995;36: 3-16.

34. New RRC, Preparation of liposomes and size determination, In: liposomes A Practical

Approch, New RRC (Ed.), Oxford; (1990); 36-39.

35. Toll R, Jacobi U, Richter H, lademann J, Schaefer H, Blume U, Penetration profile of

microspheres in follicular targeting of terminal hair follicles, J. Invest. Dermatol; (2004);

123: 168-176.

36. Donatella P, Giuseppe L, Domenico M, Franco A, Massimo F, Ethosomes for skin

delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human

skin and in vivo anti-inflammatory activity on human volunteers, Journal of controlled

release; (2005); 106(1): 99-110.

37. Vanden B, Swartzendruber V, Geest J, Development of an optimal protocol for the

ultrastructural examination of skin by transmission electron microscopy. J. Microscopy;

(1997); 187(2): 125-133.

38. Banga A.K, Chein Y.W. Hydrogel – based iontotheraputic delivery devices for

transdermaldelivery of peptide/ protein drugs. Pharmaceutical Research 1993;10: 697 –

702.

39. Biju S S, Sushama T, Mishra P R, Khar R K. Vesicular systems: An overview. Ind. J.

Pharma. Sci. 2006;68 (2): 141-153.

40. Jia-You F, Chi-Tzong H, Wen-Ta C, Ying-Yue W. Effect of liposomes and niosomes on

skin permeation of enoxacin. Int. J. Pharma. 2001; 219 (1): 61 – 72.

41. Spruance SL, Semin, “The natural history of recurrent oral facial herpes simplex virus

infec tion”, Dermatol, 1992, 11, 200-206.




42. Fiddan AP, Yeo JM, Strubbings R, Dean D, “Vesicular Approach for Drug Delivery into

or Across the Skin”, Br. Med. J., 1983, 286, 1699.

43. Fang J, Hong C, Chiu W, Wang Y, “Effect of liposomes and niosomes on skin

permeation of enoxacin”, Int. J. Pharm., 2001, 219, 61-72.

44. Johnsen SG, Bennett EP, Jensen, VG Lance,“Therapeutic effectiveness of oral

testosterone” 1974, 2, 1473-1475.

45. A. E. Buhl, D. J. Waldon, C. A. Baker, G. A. Johnson.J Invest Dermatol, Minoxidil

sulfate is the active metabolite that stimulates hair follicles. 1990 Nov;95(5):553

46. Toutitou E, Dayan N, Bergelson L, Godin B, Eliaz, M. Ethosomes novel vesicular

carriers for enhanced delivery, characterization and skin penetration properties. Journal of

Control Release, 2000; 65: 403 – 418.

47. Godin B, Touitou E, Rubinstein F, Athamna A, Athamna M. A new approach for

treatment of deep skin infections by an ethosomal antibiotic preparation: an in vivo study.

Journal of Antimicrobial Chemotherapy, 2005; 55(6): 989 – 994.

48. Jain S, Jain P, Jain NK. Transfersomes: a novel vesicular carrier for enhanced

transdermal delivery: development, characterization and performance evaluation. Drug

Development and Industrial Pharmacy, 2003, 29: 1013 – 1026.

49. Schreier H, Bovwstra J. Liposomes and niosomes as topical drug carriers: dermal and

transdermal drug delivery. Journal of Control Release 1994; 30: 1 – 15.

50. Kim S, Chien YW. Toxicity of cationic lipids and cationic polymers in gene delivery J.

Control. Release. 1996; 40: 67-76.

51. Spruance, S.L. Semin The natural history of recurrent oral facial herpes simplex virus

infec tion. Dermatol. 1992; 11:200-206.




52. Verma P, Pathak K, “Therapeutic and cosmeceuticals potential of ethosomes: An

overview”, J Adv PharmTech Res, 2010, 1, 274-82.

53. Kumar KP, Radhika PR, Sivakumar T, “Ethosomes-APriority in Transdermal Drug

Delivery”, InternationalJournal of Advances in Pharmaceutical Sciences,2010, 1, 111-

121.

54. Elka Touitou, Dayan Nava. Carriers for skin delivery of trihexyphenidyl HCl:ethosomes vs. liposomes Biomaterials 21 (2000) 1879-1885

2).pdf · review article ravi b patel et.al / ijipsr / 2 (4), ... vesicular system is ... ethosomal...

Documents