Ethosomes as a Promising Delivery Carrier for Herbal Drugs: Recent Developments


Jobin Jose, Shweta Shetty, Sandeep D S, Prashanth Nayak

Department of Pharmaceutics, N.G.S.M. Institute of Pharmaceutical Sciences, Nitte University, Paneer, Deralakatte, Mangalore-575 018

*Corresponding Author E-mail:



In the recent years of development, herbal drugs are becoming the promising tool for the cure of many diseases with the less toxic effects, better therapeutic effect, have good patience compliance. To minimize a problems of the stability, toxicity, poor bioavailability various novel drug delivery system such as phytosomes, ethosomes, herbal transdermal patches, nanoparticles etc. are used nowadays. Hence to deliver the drug at the particular site, the prompt carrier used is ethosomes. Ethosomes are developed by mixture of phospholipids and ethanol in which the ethanol concentration is maintained at higher level. This carrier will penetrate into the skin deeply to improve the delivery of drugs in to deeper layers of the skin. Ethosomes is non invasive vesicles and are commonly formulated as a carrier for the delivery of the herbal drugs into deeper layers of the skin. Thus the present review focuses on herbal ethosomes and its recent developments in drug delivery systems.


KEYWORDS: Ethosomes, Herbal drugs, Ethanol effect



The oral drug delivery system has number of disadvantages like first pass metabolism, drug degradation by enzymes, and irritation of gastro intestinal mucosa1. Thus to overcome the above problems, transdermal route is highly preferred for the delivery of drugs2. Ethosomes are the lipid form of vesicles which contains phospholipids, alcohols as their main active agents and the other agents like polyglygols, cholesterols and dye3. Skin is mainly composed of three layers such as subcutaneous layer, dermis and epidermis layer. Improved skin delivery of drugs can be attained by novel lipid carriers called as Ethosomes4,5. Ethosomes can act as excellent carrier in transdermal delivery of drugs6, 7.


Ethosomes are significantly differs from drug carriers like liposomes8. When compared to the liposomes, the ethosomal drug carrier have the greater penetration rate through the skin thus ethosomes can be usually used in the place of liposomes9. The main reason provided that is responsible for the penetration of drugs into deeper layers of skin might be due to its combined effect of both phospholipids and ethanol which is present in higher concentration in the ethosomal drug carrier10. There are various methods which are used to improve the permeation of drugs through the skin such as use of various physical and chemical methods like sonophoresis, iontophoresis etc.and also by the use of permeation enhancers11. The ethosomes are the flexible vesicles and are non invasive drug delivery carriers. Ethosomes are capable of entrapping the molecules of drug with different physicochemical characteristics like lipophilic, hydrophilic and amphiphilic12. The ethosomes particles will vary in the size range between tens nanometer to microns which will penetrate the drug through the skin layers more readily and rapidly and hence possess the higher transdermal flux13. Thus ethosomes are interesting and more innovative form of drug delivery systems that have high importance in the field of pharmaceutical technology and drug delivery in the recent years14. Further the better technologies have been developed to deliver the drug molecules with the safe penetration enhancers with the use of vesicular carriers such as ethosomes15, 16.



Figure 1: structure of ethosome vesicle


Composition of Ethosomes:

As it is mentioned that the ethosomes are mainly formulated with the combination of the phospholipids, water and ethanol in which ethanol present in greater concentration17.

·        Various phospholipids are used in formation of vesicles such as phosphotidyilcholin, phosphatidic acid, phosphatidylserine etc usually in the range of 0.7%-10%w/w.

·        Polyglycols like transcutol RTM, polyglycols etc are used to enhance the penetration of drugs through skin.

·        Ethanol, isopropyl alcohol in the ethosome provides smoothness to the vesicle membrane18.

·        Cholesterol is also used in the preparation in the range of 0.1%-1% provide stability to the vesicle membrane19

·        Then it also contains the alcohol (ethanol etc) in the concentration range in between 20% to 50% of alcohol.

·        Non ionic surfactants can be combined with the phospholipids in this preparation20.


Preparation of Herbal Ethosomes:

There are four methods of preparation of herbal ethosomes are21:

1.      Cold method

2.      Hot method

3.      Classic mechanical dispersion method

4.      Classic method.


Advantages of Ethosomal Drug Delivery:

·        Increase in the skin penetration of the drug22

·        The ethosomal drug delivery system is more inert form

·        Ethosomal formulation is also known for delivery of large and miscellaneous groups of drugs, proteins and peptides etc23.

·        Because of the presence of secured compositions in the ethosomes, this is accepted for pharmaceutical and cosmetical use also24.

·        Ethosomes contains non toxic materials in formulation hence it’s a safe drug carrier

·        The ethosomal formulations are meant to be prepared in the semisolid form either in the form of gel or in the form of cream so that it can be administered easily

·        The preparation of herbal ethosomal formulation is simple, when compared with other complicated methods25.



·        Ethosomal drug delivery system is not meant for administration of rapid bolus type drug delivery and it is usually meant for slow and sustained drug release.

·        The size of the drug molecules should be reasonable such that it should be absorbed from the outer layer of the skin

·        Yield of the formulation is very poor and hence may not be economical.

·        Skin irritation or dermatitis can take place in some patients due to penetration enhancer or excipients used.

·        No target specificity in the few formulations25.


Properties of Ethosomes:

Effect of high alcohol concentration:

Ethanol is known to be a permeation enhancers and it will fluidizes the ethosomal lipid layer it will make the outer layer most smooth such that it can penetrate in to lipids layers26. The existence of ethanol in higher concentration approximately in the range between 20-50% was the main reason to increase in the drug permeation through the skin and the molecules are less firmly packed than any other conventional vesicles but it also has the equal solubility and stability better than many other drugs. Thus the ethosomal formulation can be varied by changing the ratio of the components that are present in the formulation mainly phospholipids. As the concentration of ethanol decreases, the size of the size of ethosomes vesicles goes on increasing27.


The probable mechanism for the drug penetration had been established. It is known that the primary mechanism is due to presence of ethanol effect whereby interruption of the ethanol into intercellular lipids increases fluidity of the lipids and thus it decreases the concentration of the lipid multilayer or lipid bilayer. This is followed by secondary step by the effect of the ethosomes that comprise of inter lipid penetration and permeation of drugs through aperture of new pathways due to flexibility, softness and fusion of ethosomes with skin lipids, resulting in release of drugs in deeper layer of the skin membrane28. The absorption of the drugs occurs mainly in 2 forms


Ethanol effect:

Ethanol will act as penetration enhancers all the way through the skin. The mechanisms of increase in the penetration of drug through skin are well recognized. Ethanol will penetrate into intracellular lipids and increases the variability of cell membrane lipid layer. Thus ethanol will be considered as main constituents of the ethosomal formulation29.


Ethosome effect:

As the fluidity of the cell membrane increases by ethanol, ethosomes causes increase in skin permeability. Thus the ethosomes will very easily penetrate inside the deeper layer of the skin, where it gets combined with skin lipids and release the herbal drugs30.


Applications of ethosomes.




Gives enhanced skin penetration

Enhanced the biological activity

Better pharmacodynamic activity


Selective release of drug to preferred site for extended period of time


Provide control release of drugs to the required site

Provides considerable decrease in the blood glucose level


Enhanced dermal deposition

Improved bioavailability of drugs

Increase in the intracellular drug delivery system

Anti-HIV agents



Increased in the biological action for about two to three times

Shows decrease in the drug toxicity

Improved transdermal flux


Shows good appearance of genes

Targeted to the selective site only

Better drug delivery through the skin

Trihexyphenidyl hydrochloride

Provides controlled release of the drug to desired site

Better patient compliance

It also improves the transdermal flux

Shows increase in the biological activity of the drugs and dosage form

Curcuma longa

Improved bioavailability

Improved increase in permeability

Glycyrrhiza glabra

Improved anti-inflammatory activity

Sustained release action

Increase penetration to skin

Cannabis sativa

Improved patient compliance

Increased skin permeation.



There is great potential in development of the drug carriers like ethosomes for the delivery of the drugs at particular site or into deeper layer of the skin for herbal formulations. It is safe, effective, convenient and economically affordable drug delivery. As the drug go through into the deeper layer of the skin it results in a enhance efficiency and make it more bio available by increasing the solubility, controlled release and target oriented. The applications of these ethosomes to natural medicines will lead to protection from the GI degradation which cannot be obtained through conventional drug delivery system because of large molecular size, poor solubility etc. Hence it can be concluded that the ethosomes acts as good and most relevant carrier for the herbal formulations for the delivery of the drugs.



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Received on 03.12.2017          Modified on 18.01.2018

Accepted on 24.02.2018        © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(7): 3197-3200.

DOI: 10.5958/0974-360X.2018.00587.5