Ethosome Explained

Ethosomes are phospholipid nanovesicles used for dermal and transdermal delivery of molecules. Ethosomes were developed by Touitou et al.,1997, as additional novel lipid carriers composed of ethanol, phospholipids, and water. They are reported to improve the skin delivery of various drugs. Ethanol is an efficient permeation enhancer that is believed to act by affecting the intercellular region of the stratum corneum. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol (relatively high concentration), and water. These soft vesicles represent novel vesicles carriers for enhanced delivery through the skin. The size of the ethosomes vesicles can be modulated from tens of nanometers to microns.^[1]

Structure and composition

Ethosomes are mainly composed of multiple, concentric layers of flexible phospholipid bilayers, with a relative high concentration of ethanol (20-45%), glycols and water.^{[2] [3]} Their overall structure has been confirmed by ³¹P-NMR, EM and DSC. They have high penetration of the horny layer of the skin, which enhances the permeation of encapsulated drugs. The mechanism of permeation enhancement is attributed to the overall properties of the system.^{[4] [5]}

Applications

Because of their unique structure, ethosomes are able to efficiently encapsulate and deliver into the skin highly lipophilic molecules such as testosterone, cannabinoids and ibuprofen, as well as hydrophilic drugs such as clindamycin phosphate, buspirone hydrochloride. They have been studied for the transdermal and intradermal delivery of peptides, steroids, antibiotics, prostaglandins, antivirals and anti-pyretics.^{[6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]} The components used to make ethosomes are already approved for pharmaceutical and cosmetic use and the formulated vesicles are stable when stored. They can be incorporated in various pharmaceutical formulations such as gels, creams, emulsions and sprays. They're consequently being developed for pharmaceutical and cosmeceutical products.^{[17] [18] [19] [20] [21] [22] [23]} Ethosomal systems compare favourably to alternative carriers for quantity and depth of molecule delivery.^{[24] [25] [26] [27] [28] [29] [30]}

Notes and References

1. Verma. Poonam. Pathak. K.. 2010. Therapeutic and cosmeceutical potential of ethosomes: An overview. Journal of Advanced Pharmaceutical Technology & Research. 1. 3. 274–282. 10.4103/0110-5558.72415. 2231-4040. 3255417. 22247858 . free .
2. Touitou E. Compositions for applying active substances to or through the skin; Patent number: 5540934 Granted 1996
3. Touitou E. Composition for applying active substances to or through the skin; Patent number 5716638 Granted 1998
4. Dayan, N., Touitou, E. (2000) Carriers for Skin Delivery of Trihexyphenidyl HCl: Ethosomes vs. Liposomes. Biomaterials, 21:1879-1885.
5. Touitou, E., Dayan, N., Bergelson, L., Godin, B., Eliaz, M. (2000) Ethosomes-Novel Vesicular Carriers for Enhanced Delivery: Characterization and Skin Penetration Properties, J. Control. Release, 65:403-418.
6. Horwitz, E., Pisanty, S., Czerninski, R., Helser, M., Eliav, E., Touitou, E. (1999) A Clinical Evaluation of a Novel Liposomal Carrier for Aciclovir in the Topical Treatment of Recurrent Herpes Labialis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 88: 700-705.
7. Lodzki, M., Godin, B., Rakou, L., Mechoulam, R., Gallily, R., Touitou, E. (2003) Cannabidiol Transdermal Delivery and Anti-Inflammatory Effect in a Murine Model. J. Control. Release, 93: 379-389
8. Godin, B., Touitou, E. (2004) Mechanism of Bacitracin Permeation Enhancement through the Skin and Cellular Membranes from an Ethosomal Carrier. J. Control. Release, 94:365-79.
9. Godin, B., Touitou, E., Rubinstein, E., Athamna, A., Athamna, M. (2005) A New Approach for Treatment of Deep Skin Infections by An Ethosomal Antibiotic Preparation: An In Vivo Study. J. Antimicrob. Chemother., 55: 989-994.
10. Godin, B., Touitou, E. (2005) Erythromycin Ethosomal Systems: Physicochemical Characterization and Enhanced Antibacterial Activity. Cur. Drug Deliv., 2: 269-275.
11. Touitou, E., Godin, B., Shumilov, M., Bishouty, N., Ainbinder, D., Shouval, R., Ingber, A., Leibovici, V. (2007) Efficacy and tolerability of clindamycin phosphate and salicylic acid gel in the treatment of mild to moderate acne vulgaris. J. Eur. Acad. Dermatol. Venerol., 2008 May;22(5):629-631.
12. Ainbinder D, Protokin R, Chaouat M, Touitou E. (2009) Effect of honokiol and 5-FU on non-melanoma skin cancer cells, J. Drug Del. Sci. Tech., 19: 283-7.
13. Shumilov M, Touitou E. (2010) Buspirone transdermal administration for menopausal syndromes, in vitro and in animal model studies. Int J Pharm. 387:26-33.
14. Shumilov M, Bercovich R, Duchi S, Ainbinder D, Touitou E. (2010) Ibuprofen Transdermal Ethosomal Gel: Characterization and Efficiency in Animal Models. J. Biomed. Nanotechnol., 6: 569-576.
15. Ainbinder, D., Touitou, E. (2005) Testosterone Ethosomes for Enhanced Transdermal Delivery. Drug Deliv., 12: 297-303.
16. Touitou, E., Godin, B., Dayan, N., Piliponsky, A., Levi-Schaffer, F., Weiss, C. (2001) Intracellular Delivery Mediated by an Ethosomal Carrier. Biomaterials, 22: 3053-9.
17. Touitou, D., Godin, B., Touitou, E. (2005) Ethosomes- Efficiently Delivering Active Agents to Skin. Personal Care, 71-3.
18. Ainbinder, D., Godin, B., Touitou, E. (2016) Ethosomes: Enhanced delivery of drugs to and across the skin. In: Dragicevic, Nina, Maibach and Howard I (Eds) Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Nanocarriers. pp. 61-75, Springer, Berlin Heidelberg.
19. Godin, B., Touitou, E. (2015) Dermal and transdermal delivery. In: Bhushan (Ed) Encyclopedia of Nanotechnology, pp. 1-12, Springer, Netherlands.
20. Godin, B., Touitou, E. (2012) Dermal and transdermal delivery. In: Bhushan and Decuzzi (Eds) Encyclopedia of nanotechnology, pp 517-526, Springer.
21. Godin, B., Touitou, E. Nanoparticles aiming at specific targets – dermal and transdermal delivery. (2007) In: Domb, Tabata, Ravi Kumar and Farber (Eds) Nanoparticles for Pharmaceutical Applications, pp. 191-212, American Scientific Publishers, Valencia.
22. Touitou, E., Godin, B. (2006) Vesicles for enhanced delivery into and through the skin. In: Touitou and Barry (Eds) Enhancement in drug delivery, pp. 37-56, CRC Press, Taylor & Francis Group, Boca Raton-London-New York.
23. Touitou, E., Godin, B. (2005) Enhanced skin permeation using ethosomes. In: Smith and Maibach (Eds) Percutaneous Penetration Enhancers, Second Edition, pp. 95-108 CRC Press, New York.
24. Wilson V, Siram K, Rajendran S, Sankar V. (2017) Development and evaluation of finasteride loaded ethosomes for targeting to the pilosebaceous unit. Artif Cells Nanomed Biotechnol., 1-10.
25. Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. (2005) Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release., 106: 99-110.
26. Jain S, Tiwary AK, Sapra B, Jain NK. (2007) Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS Pharm Sci Tech., 21;8: E111.
27. Mao X, Cheng X, Zhang Z, Wang Z, Wang Z. (2017) The therapy with ethosomes containing 5-fluorouracil for laryngotracheal stenosis in rabbit models. Eur Arch Otorhinolaryngol., 274:1919-24.
28. Esposito E, Drechsler M, Huang N, Pavoni G, Cortesi R, Santonocito D, Puglia C. (2016) Ethosomes and organogels for cutaneous administration of crocin. Biomed Micro devices., 18:108.
29. Akhtar N, Varma A, Pathak K. (2016) Ethosomes as Vesicles for Effective Transdermal Delivery: From Bench to Clinical Implementation. Curr Clin Pharmacol., 11: 168-90.
30. Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. (2005) Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release., 106:99-110.