Need of ethosomes as a transdermal drug delivery system

Vaishnavi Inde¹*, Mahesh Kadare¹, Vinod Matole¹, Doke Patil², Amar Anil²,

Harshada Patil³, Sneha Kashid⁴, Kajal wani⁴

¹Shivai Charitable Trust’s College of Pharmacy, Koregaonwadi, Omerga.

²SVSPM’s Arya college of Pharmacy.

³MSS's College of Pharmacy, Medha.

⁴Poona College of Pharmacy, BVDU.

*Corresponding Author E-mail:

ABSTRACT:

Transdermal Drug Delivery (TDD) TDD is a painless method of delivering drugs systemically by applying a drug formulation onto intact and healthy skin. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol (relatively high concentration) and water. In vitro and in vivo skin permeation experiments have shown that ethosomal formulations can improve the penetration of both hydrophobic and hydrophilic compounds when compared to traditional liposomes. Cold method and hot method are the two types of method of preparation of ethosomes. In comparison to traditional liposomes, antigen-loaded ethosomes for transcutaneous immunization against Hepatitis B were synthesized and described, demonstrating better entrapment effectiveness, appropriate size range, and a unilamellar, spherical shape.As a topical medium (gel), ethosomes and liposomes of azelaic acid (an anti-keratinizing agent used in the treatment of acne) were created, and the results showed that ETHOS 40 might be responsible for a larger azelaic acid concentration than ETHOS 20 and liposomes.

KEYWORDS: Ethosomes, Drug delivery, Novel drug delivery, Transdermal drug delivery.

INTRODUCTION:

Nowadays, transdermal drug delivery system is easiest way to deliver drug via protective barrier i.e. skin. The hydro alcoholic or hydro/alcoholic/glycolic phospholipid that makes up the ethosome as a vesicular carrier, and the concentration of alcohols or their combination is relatively high.^1-2

These types of systems are newer carriers of lipid vesicles.

Phospholipids with various chemical structures such as 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 Such a formulation allows for the administration of large concentrations of active substances through the skin. The alcohol: water or alcohol-polyol:water ratio can be changed to regulate drug delivery. Cholesterol at quantities ranging from 0.1 to 1% can also be added to the mixture. Non-ionic surfactants (PEG-alkyl ethers) can also be mixed with the phospholipids in these formulations.^3-5

The high ethanol concentration distinguishes the ethosomes, as ethanol is renowned for disrupting skin lipid bilayer architecture; thus, when incorporated into a vesicle membrane, vesicles have the capacity to enter the stratum corneum. Furthermore, due to 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 by disturbing the stratum corneum lipid. ^6-7

One of the most essential characteristics of ethosomal formulation is its continuous release. The ethosomal formulation significantly prolonged zidovudine release through the artificial membrane when compared to the drug solution. The cumulative amount of zidovudine released from the ethosomal formulation in 24 hours was 38.4 1.2%, compared to 92.5 2.1% from the drug solution.

In vitro and in vivo skin permeation experiments have shown that ethosomal formulations can improve the penetration of both hydrophobic and hydrophilic compounds when compared to traditional liposomes. Several researchers have observed that medications synthesized in ethosomes penetrate the skin 5-10 times better than traditional liposome formulations.^8-10

Methods of preparations of Ethosomes-

As detailed below, ethosomal formulation can be produced either hot or cold. Both procedures are simple, do not require sophisticated equipment, and are easily scaled up to industrial levels.

1. Cold method –

In this procedure Phospholipids, drugs, and other lipid compounds are dissolved in ethanol in a covered vessel at room temperature using a mixer and rapid agitation. During the stirring process, propylene glycol or another polyol is introduced.In a water bath, this mixture is heated to 300 degrees Celsius. In a separate saucepan, water heated to 300°C is added to the mixture, which is then agitated for 5 minutes in a covered vessel. Using probing sonication or extrusion, the ethosomal formulation’s vesicle size can be reduced to the desired extent. Finally, the formulation is refrigerated.¹¹

The vesicle size of the ethosomal formulation can be decreased if desired, to extend using the sonication or extrusion.

2. Hot method -

Phospholipid is dispersed in water using this approach by heating it in a water bath at 400°C until a colloidal solution is formed.

In a separate tank, ethanol and propylene glycol are combined and heated to 400 degrees Celsius. When both combinations reach 400 degrees Celsius, the organic phase is introduced to the aqueous one. The medication is dissolved in water or ethanol depending on whether it is hydrophilic or hydrophobicUsing, the formulation can be reduced to the desired extent^.(Godin B et al., Hadgraft J. et al., Koli, J.R. et al., Touitou, E. et al.)

Physical methods such as iontophoresis, microneedles, and sonophoresis are relatively difficult to employ and will have an impact on patient compliance.¹²

Therapeutic Applications of Ethosomes-

In comparison to traditional liposomes, antigen-loaded ethosomes for transcutaneous immunization against Hepatitis B were synthesized and described, demonstrating better entrapment effectiveness, appropriate size range, and a unilamellar, spherical shape. Spectral bio imaging and flow cytometric experiments revealed that HBsAg-loaded ethosomes were efficiently taken up by murine dendritic cells in vitro, reaching a peak after 180 minutes. In comparison to conventional liposomes and soluble antigen preparations, the transcutaneous delivery capacity of the antigen-loaded antigen system employing human cadaver skin exhibited much higher antigen skin permeation.In comparison to the intramuscularly administered alum-adsorbed HBsAg suspension, the topically applied plain HBsAg solution, and the hydroethanolic (25%) HBsAg solution, the topically applied HBsAg-loaded ethosomes elicited a robust systemic and mucosal humoral immune response. HBSAg-loaded ethosomes can elicit a protective immune response, and their ability to traverse and target the immunological milieu of the skin could be used to develop a transcutaneous vaccine against Hepatitis B virus.¹¹Hormone delivery via mouth is associated with problems such as rapid first pass metabolism, low oral bioavailability, and a variety of dose-dependent adverse effects such as virilization, acne, and gynecomastia. In addition to these side effects, oral hormonal preparations are extremely dependent on patient compliance. The likelihood of treatment failure is known to increase with each dose skipped.

As a topical medium (gel), ethosomes and liposomes of azelaic acid (an anti-keratinizing agent used in the treatment of acne) were created, and the results showed that ETHOS 40 might be responsible for a larger azelaic acid concentration than ETHOS 20 and liposomes.

Osmotics Inc. in the United States reported a novel cellulite cream called lipoduction, which employed ethosome technology to penetrate the skin’s lipid barrier and deliver contents directly into fat cells. Lipoduction ingredients reduced the appearance of cellulite by up to 80% in less than 60 days._.¹³

REFERENCES:

1. Touitou, E., B. Godin and C. Weirs. Enhanced Delivery into and across the skin by Ethosomal carries, Drug Dev. Research. 2000; 50: 406-415.

2. Anuradha Patel, R.K. Sharma, Mahesh Trivedi, Shivaprakash, Anjana Panicker. Ethosomes: A Novel Tool for Transdermal Drug Delivery. Research J. Pharm. And Tech. 2013; 6(8): 838-841.

3. Touitou, E.; Godin, B.; Dayan, N.; Weiss, C.; Piliponsky, A.; Levi-Schaffer, F. Intracellular delivery mediated by an ethosomal carrier. Biomaterials. 2001; 22: 3053-3059

4. Kirjavainen M, Urtti A, Jaaskelainen I, Suhonen TM, Paronen P, Valjakka-Koskela R, Kiesvaara J, Monkkonen J. Interaction of liposomes with human skin in vitro – the influence of lipid composition and structure. Biochim Biophys Acta. 1996; 1304: 179–189.

5. Godin B, Tauitou Elka. Vesicular carrier for transdermal drug delivery system-ethosomes. Current Drug Delivery. 2005; 2: 269‐275.

6. Hadgraft J, Guy R. Transdermal Drug Delivery, Developmental Issues and Research Initiatives. New York: Marcel Dekker 1989.

7. Koli, J.R. and S. Lin. 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.

8. Touitou, E. Composition of applying active substance to or through the skin.US Patent, 1998; 5: 540-934.

9. Verma, D.D. and A. Fahr. Synergistic penetration of ethanol and phospholipids on the topical delivery of cyclosporine. J. Control Release. 2004; 97: 55-66.

10. Essa AE, Bonner MC, Barry BW. Electroporation and ultradeformable liposomes; Human skin barrier repair by phospholipids. J Cont Rel. 2003; 92: 163-72.

11. Mishra D, Mishra PK, Dubey V, Nahar M, Jain NK. Systemic and mucosal immune response induced by transcutaneous immunization using Hepatitis B surface antigen-loaded modified liposomes. J Control Release. 2007; 33: 424-33.

12. Ainbinder D, Touitou E. Testosterone ethosomes for enhanced transdermal delivery. Drug Del. 2000; 12: 297–303.

13. 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.

Received on 02.09.2023 Modified on 19.03.2024

Asian J. Pharm. Tech. 2024; 14(3):286-288.

DOI: 10.52711/2231-5713.2024.00046