Ethosomes: nanostructures for enhanced skin penetration

Document Type : Review Paper

Authors

1 Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, India

2 Amity Institute of Pharmacy, Amity University Haryana, Gurgaon, India

Abstract

The skin is a prominent and easily accessible organ in the human body. Despite providing the most straightforward and non-invasive drug administration method, the skin's limited permeability restricts the range of medications effectively delivered transdermally. The use of ethosomes as innovative vesicles for transdermal drug delivery has shown considerable promise in enhancing the permeation of drugs through the biological membrane. Ethosomes offer a preferable alternative to liposomes due to their ability to penetrate the skin more rapidly. Researchers have shown significant interest in ethosomes because of their exceptional capacity to deeply penetrate the skin, improve drug delivery, and achieve high entrapment efficiency. This study provides a comprehensive exploration of ethosomes as a drug delivery system. It aims to present detailed information on various aspects of ethosomes, including their manufacturing process, advantages, composition, properties, and applications in treating multiple diseases such as rheumatoid arthritis, psoriasis, hormonal imbalances, and other skin infections.

Keywords

References

  1. Abdulbaqi IM, Darwis Y, Khan NAK, Assi RA, Khan AA. Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials. Int J Nanomedicine. 2016;11:2279-2304.
  2. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14(2):101-114.
  3. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261-1268.
  4. Scheindlin S. Transdermal drug delivery: past, present, future. Mol Interv. 2004;4(6):308-312.
  5. Mezei M, Gulasekharam V. Liposomes—a selective drug delivery system for the topical route of administration: I. Lotion dosage form. Life Sci. 1980;26(18):1473-1477.
  6. Pierre MBR, Costa ISM. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch Dermatol Res. 2011;303(9):607-621.
  7. Siler-Marinkovic S. Liposomes as drug delivery systems in dermal and transdermal drug delivery. In: Dragicevic N, Maibach HI, editors. Percutaneous Penetration Enhancers: Chemical Methods in Penetration Enhancement. Berlin, Heidelberg: Springer; 2016; 15-38.
  8. Tapfumaneyi P, Imran M, Mohammed Y, Roberts MS. Recent advances and future prospective of topical and transdermal delivery systems. Front Drug Deliv. 2022;2:957732.
  9. Touitou E, Godin B. Ethosomes for skin delivery. J Drug Deliv Sci Technol. 2007;17(5):303-308.
  10. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000;65(3):403-418.
  11. Patrekar PV, Inamdar SJ, Mali SS, Mujib MT, Ahir AA, Hosmani AH. Ethosomes as novel drug delivery system: a review. The Pharma Innovation Journal. 4, 9, 2015; 10-21.
  12. Kumar A, Dubey A. Ethosomes: a novel approach in transdermal drug delivery system. Int J Pharmacy and Life Sciences. 2020;11(5):6598-6608.
  13. Romero EL, Morilla MJ. Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations. Int J Nanomedicine. 2013;8:3171-3186.
  14. Sala M, Diab R, Elaissari A, Fessi H. Lipid nanocarriers as skin drug delivery systems: properties, mechanisms of skin interactions and medical applications. Int J Pharm. 2018;535(1-2):1-17.
  15. Chauhan N, Vasava P, Khan SL, Siddiqui FA, Islam F, Chopra H, et al. Ethosomes: a novel drug carrier. Ann Med Surg. 2022;80:104595.
  16. Zhang Z, Wo Y, Zhang Y, Wang D, He R, Chen H, et al. In vitro study of ethosome penetration in human skin and hypertrophic scar tissue. Nanomedicine. 2012;8(6):1026-1033.
  17. Mishra D, Mishra PK, Dabadghao S, Dubey V, Nahar M, Jain NK. Comparative evaluation of hepatitis B surface antigen-loaded elastic liposomes and ethosomes for human dendritic cell uptake and immune response. Nanomedicine. 2010;6(1):110-118.
  18. Zhou Y, Wei Y, Liu H, Zhang G, Wu X. Preparation and in vitro evaluation of ethosomal total alkaloids of Sophora alopecuroides loaded by a transmembrane pH-gradient method. AAPS PharmSciTech. 2010;11(3):1350-1358.
  19. Ascenso A, Raposo S, Batista C, Cardoso P, Mendes T, Praça FG, et al. Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. Int J Nanomedicine. 2015;10:5837-5851.
  20. Zhang JP, Wei YH, Zhou Y, Li YQ, Wu XA. Ethosomes, binary ethosomes and transfersomes of terbinafine hydrochloride: a comparative study. Arch Pharm Res. 2012;35(1):109-117.
  21. Finnin BC, Morgan TM. Transdermal penetration enhancers: applications, limitations, and potential. J Pharm Sci. 1999;88(10):955-958.
  22. Yang Y, Wu F, Liu J, Fan L, Zhu Y, Zhai G. A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use. Drug Dev Ind Pharm. 2015;41(11):1782-1788.
  23. Bragagni M, Mennini N, Maestrelli F, Cirri M, Mura P. Comparative study of liposomes, transfersomes and ethosomes as carriers for improving topical delivery of celecoxib. Drug Deliv. 2012;19(7):354-361.
  24. Touitou E. Composition for applying active substances to or through the skin. US Patent 5716638A. 1998.
  25. Abu-Huwaij R, Zidan AN. Unlocking the potential of cosmetic dermal delivery with ethosomes: a comprehensive review. J Cosmet Dermatol. 2024;23(1):17-26.
  26. Song CK, Balakrishnan P, Shim CK, Chung SJ, Chong S, Kim DD. A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: characterization and in vitro/in vivo evaluation. Colloids Surf B Biointerfaces. 2012;92:299-304.
  27. Jafari A, Daneshamouz S, Ghasemiyeh P, Mohammadi-Samani S. Ethosomes as dermal/transdermal drug delivery systems: applications, preparation and characterization. J Liposome Res. 2023;33(1):34-52.
  28. Zahid SR, Upmanyu N, Dangi S, Ray SK, Jain P, Parkhe G. Ethosome: a novel vesicular carrier for transdermal drug delivery. J Drug Deliv Ther. 2018;8(6):318-326.
  29. Gangwar S, Singh S, Garg G. Ethosomes: a novel tool for drug delivery through the skin. J Pharm Res. 2010;3(4):688-691.
  30. Nikalje AP. Ethosomes: a novel tool for transdermal drug delivery. Int J Res Pharm Sci. 2012;2(1):1-20.
  31. Zahid SR, Upmanyu N, Dangi S, Ray SK, Jain P, Parkhe G. Ethosome: a novel vesicular carrier for transdermal drug delivery. J Drug Deliv Ther. 2018;8(6):318-326.
  32. Chen M, Gupta V, Anselmo AC, Muraski JA, Mitragotri S. Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers. J Control Release. 2014;173:67-74.
  33. Paiva-Santos AC, Silva AL, Guerra C, Peixoto D, Pereira-Silva M, Zeinali M, et al. Ethosomes as nanocarriers for the development of skin delivery formulations. Pharm Res. 2021;38(6):947-970.
  34. Razavi H, Janfaza S. Ethosome: a nanocarrier for transdermal drug delivery. Arch Adv Biosci. 2015;6(2):38-43.
  35. Shahwal VK, Samnani A, Dubey BK, Bhowmick M. Ethosomes: an overview. Int J Biomed Adv Res. 2011; 2(5):159-166.
  36. Ascenso A, Raposo S, Batista C, Cardoso P, Mendes T, Praça FG, et al. Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. Int J Nanomedicine. 2015;10:5837-5851.
  37. Pandey V, Golhani D, Shukla R. Ethosomes: versatile vesicular carriers for efficient transdermal delivery of therapeutic agents. Drug Deliv. 2015;22(8):988-1002.
  38. Pakhale NV, Gondkar SB, Saudagar RB. Ethosomes: transdermal drug delivery system. J Drug Deliv Ther. 2019;9(3):729-733.
  39. Verma P, Pathak K. Therapeutic and cosmeceutical potential of ethosomes: an overview. J Adv Pharm Technol Res. 2010;1(3):274-282.
  40. Agrawal G, Chouthe R, Damale M, Kulkarni D, Panzade P, Pathan I, et al. Ethosomes: an exciting and promising alcoholic carrier system for treating androgenic alopecia. In: Androgenic Alopecia. IntechOpen; 2018.
  41. Cevc G, Schätzlein A, Blume G. Transdermal drug delivery: Innovative transdermal delivery using ultradeformable vesicles. Eur J Pharm Biopharm. 2003; 58(2):281-299.
  42. Zhou Y, Wei Y, Liu H, Zhang G, Wu X. Preparation and in vitro evaluation of ethosomal total alkaloids of Sophora alopecuroides loaded by a transmembrane pH-gradient method. AAPS PharmSciTech. 2010;11(3):1350-1358.
  43. Zhang Z, Chen Y, Xu H, Wo Y, Zhang Z, Liu Y, et al. 5-Aminolevulinic acid loaded ethosomal vesicles with high entrapment efficiency for in vitro topical transdermal delivery and photodynamic therapy of hypertrophic scars. Nanoscale. 2016;8(46):19270-19279.
  44. Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. 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. 2005;106(1-2):99-110.
  45. Akiladevi D, Basak S. Ethosomes – a noninvasive approach for transdermal drug delivery. Int J Curr Pharm Res.2013; 2(4):1-4.
  46. Mishra D, Balekar N, Dhote V, Mishra P. Ethosomes: a novel carrier for dermal or transdermal drug delivery. In: Recent Advances in Novel Drug Carrier Systems. 2017: 1-26.
  47. López-Pinto JM, González-Rodríguez ML, Rabasco AM. Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes. Int J Pharm. 2005;298(1):1-12.
  48. Yang L, Wu L, Wu D, Shi D, Wang T, Zhu X. Mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes. Int J Nanomedicine. 2017;12:3357-3364.
  49. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000;65(3):403-418.
  50. Indira S, Reddymalla P, Srinivas P. Formulation and evaluation of ethosomal topical gels of etoricoxib. Int J Pharm Res Scholars. 2015;4(4):93-103.
  51. Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J Control Release. 2007;123(2):148-154.
  52. Jain S, Tiwary AK, Sapra B, Jain NK. Ethosomes as elastic vesicles in transdermal drug delivery: an overview. Int J Pharm Sci Res. 2012;3(4):1-10.
  53. Soba SV, Babu M, Panonnummal R. Ethosomal gel formulation of alpha phellandrene for the transdermal delivery in gout. Adv Pharm Bull. 2021;11(1):137-149.
  54. Dhakar RC. Formulation development and evaluation of ethosome of stavudine. Indian J Pharm Edu Res. 2021.
  55. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000;65(3):403-418.
  56. Bendas ER, Tadros MI. Enhanced transdermal delivery of salbutamol sulfate via ethosomes. AAPS PharmSciTech. 2007;8(4):E107.
  57. Godin B, Touitou E. Erythromycin ethosomal systems: physicochemical characterization and enhanced antibacterial activity. Curr Drug Deliv. 2005;2(3):269-275.
  58. Zhu X, Li F, Peng X, Zeng K. Formulation and evaluation of lidocaine base ethosomes for transdermal delivery. Anesth Analg. 2013;117(2):352-357.
  59. Jaiswal PK, Kesharwani S, Kesharwani R, Patel DK. Ethosome: a new technology used as topical & transdermal delivery system. J Drug Deliv Ther. 2016;6(3):7-17.
  60. Jain S, Tiwary AK, Sapra B, Jain NK. Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS PharmSciTech. 2007;8(4):E111.
  61. Mohanty D, Mounika A, Bakshi V, Haque MA, Sahoo CK. Ethosomes: a novel approach for transdermal drug delivery. Int J Chem Tech Res. 2018;11(8):219-226.
  62. Akib NI, Novianti C, Ritonga H, Apt S, Adjeng AN. Optimization of method and proportion of phosphatidylcholine and ethanol for preparation of kojic acid ethosome. Res J Pharm Technol. 2020;13(11):5251-5256.
  63. Havaldar VD, Mali SS, Mali KK, Shinde SS, Jadhav NY, Shinde AA. Ethosomes: an overview. Int J Med Pharm Res. 2012;2(5):1-8.
  64. El-Alim SHA, Kassem AA, Basha M, Salama A. Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: in vitro and in vivo evaluation. Int J Pharm. 2019;563:293-303.
  65. Li D, Dong J, Xiong T, Zhou X, Li Y, Chen C, et al. Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout. Colloids Surf B Biointerfaces. 2024;242:114087.
  66. Ma H, Guo D, Fan Y, Wang J, Cheng J, Zhang X. Paeonol-loaded ethosomes as transdermal delivery carriers: design, preparation and evaluation. Molecules. 2018;23(7):1756.
  67. Alfehaid FS, Nair AB, Shah H, Aldhubiab B, Shah J, Mewada V, et al. Enhanced transdermal delivery of apremilast loaded ethosomes: optimization, characterization and in vivo evaluation. J Drug Deliv Sci Technol. 2024;91:105211.
  68. Aggarwal D, Jain T, Saini C, Devi N, Boora N, Murali K, et al. Enhanced delivery of herbal medications by using ethosomes. Arch Biochem Biophys. 2024;1(5):541-552
  69. Ramadhani D, Harahap Y, Sagita E, Sari KCDP, Andranilla RK, Trisina J, et al. Transdermal delivery of ketoprofen for osteoarthritis treatment and management: a literature review on current progression. Pharm Sci Res. 2024;11(1):18-26.
  70. Lodzki M, Godin B, Rakou L, Mechoulam R, Gallily R, Touitou E. Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model. J Control Release. 2003;93(3):377-387.
  71. Ahad A, Raish M, Al-Mohizea AM, Al-Jenoobi FI, Alam MA. Enhanced anti-inflammatory activity of carbopol loaded meloxicam nanoethosomes gel. Int J Biol Macromol. 2014;67:99-104.
  72. Shumilov M, Bercovich R, Duchi S, Ainbinder D, Touitou E. Ibuprofen transdermal ethosomal gel: characterization and efficiency in animal models. J Biomed Nanotechnol. 2010;6(5):569-576.
  73. Kligman AM. An overview of acne. J Invest Dermatol. 1974;62(3):268-287.
  74. Kolarsick PAJ, Kolarsick MA, Goodwin C. Anatomy and physiology of the skin. J Dermatol Nurses Assoc. 2011;3(4):203-213.
  75. Nguyen R, Su J. Treatment of acne vulgaris. Paediatr Child Health. 2011;21(3):119-125.
  76. Vishwakarma M, Haider T, Soni V. Next-generation skin cancer treatment: a quality by design perspective on artificial neural network-optimized cationic ethosomes with bleomycin sulphate. J Drug Deliv Sci Technol. 2024;96:105705.
  77. Ferrara F, Bondi A, Pula W, Contado C, Baldisserotto A, Manfredini S, et al. Ethosomes for curcumin and piperine cutaneous delivery to prevent environmental-stressor-induced skin damage. Antioxidants. 2024;13(1):91.
  78. Godin B, Touitou E. Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier. J Control Release. 2004;94(2-3):365-379.
  79. Touitou E, Godin B, Shumilov M, Bishouty N, Ainbinder D, Shouval R, et al. Efficacy and tolerability of clindamycin phosphate and salicylic acid gel in the treatment of mild to moderate acne vulgaris. J Eur Acad Dermatol Venereol. 2008;22(5):629-631.
  80. Apriani EF, Rosana Y, Iskandarsyah I. Formulation, characterization, and in vitro testing of azelaic acid ethosome-based cream against Propionibacterium acnes for the treatment of acne. J Adv Pharm Technol Res. 2019;10(2):75-80.
  81. Maheshwari RGS, Tekade RK, Sharma PA, Darwhekar G, Tyagi A, Patel RP, et al. Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: a comparative assessment. Saudi Pharm J. 2012;20(2):161-170.
  82. Fathalla D, Youssef EMK, Soliman GM. Liposomal and ethosomal gels for the topical delivery of anthralin: preparation, comparative evaluation and clinical assessment in psoriatic patients. Pharmaceutics. 2020;12(5):446.
  83. Fang Q, Li Y, Xiong F, Hu X, Song Y, Shen W, et al. Formulation and characterization of ethosomes for transdermal delivery of Prinsepia utilis rogle seed oil with ameliorative effects against UVB-induced skin damage. AAPS PharmSciTech. 2024;25(5):122.
  84. Ainbinder D, Touitou E. Testosterone ethosomes for enhanced transdermal delivery. Drug Deliv. 2005;12(5):297-303.
  85. Shumilov M, Touitou E. Buspirone transdermal administration for menopausal syndromes, in vitro and in animal model studies. Int J Pharm. 2010;387(1-2):26-33.
  86. Uchechi O, Ogbonna JD, Attama AA. Therapeutic and cosmeceutical potential of ethosomes: an overview. J Basic Clin Pharm.2011;2(1):1-8.
  87. Esposito E, Menegatti E, Cortesi R. Ethosomes and liposomes as topical vehicles for azelaic acid: a preformulation study. J Cosmet Sci. 2004;55(3):253-264.
  88. Upadhyay N, Mandal S, Bhatia L, Shailesh S, Chauhan P. A review on ethosomes: an emerging approach for drug delivery through the skin. Recent Res Sci Technol. 2011;3(7):19-24.
  89. Farhath S, Fels S, Athira J, Syamasree S, Neena P, et al. Ethosome: a novel approach to enhance drug permeation. Int J Pharm Sci Rev Res. 2019;55(1):18-22.
  90. Pang D. Use of decorin in a cosmetic or dermatologic composition. US Patent US20030124152A1. 2003.
  91. Selner M. Method for treating inflammatory skin conditions and other topical conditions or disorders. US Patent US20050287185A1. 2005.
  92. Preparation technology and application of composite ceramide liposomes. CN Patent CN115919680A. 2023.
  93. Kim YM, Jang GH. Method of preparing bioactive substance-encapsulated ethosome, ethosome composition, and cosmetic composition including ethosome composition. US Patent US11452679B2. 2022.
  94. Ahmed TA, Alzahrani MM, Alhakamy NA, Felimban RI. Ketoconazole ophthalmic preparations containing trans-ethosomal drug nanoparticles. US Patent US11285148B1. 2022.
  95. Awad SM. Formulation of retinyl palmitate-loaded topical ethosomes for treatment of acne vulgaris: a split-face comparative clinical study. Clinical Trials.gov. 2022.
  96. Jun YJ, Kim HJ. Ethosomal composition including ethosomes encapsulating vitamin and dexpanthenol and method for preparing the same. AU Patent AU2020389480A1. 2021.
  97. Karatoprak G, Yucel C, Baskal G. An anti-aging cosmetic product. WO Patent WO2021040645A1. 2021.
  98. 9A kind of gel skin care item and preparation method thereof containing NMN. CN Patent CN108969396A. 2018.
  99. Agrawal G, et al. Poloxamer based in-situ nasal gel of naratriptan hydrochloride deformable vesicles for brain targeting. AU Patent AU2021107008A4. 2021.
  100. Hu C, Liu Y, Zhao W, Wang J. Capsaicin ethosomes gel and preparation method thereof. CN Patent CN106074365A. 2016.
  101. Hu C, Liu Y, Wang J, Li R. Tretinoin ethosomes gel and preparation method thereof. CN Patent CN104983675A. 2015.
  102. Lu J, Guo T, Fan Y, Li Z, He Z, Yin S, et al. Recent developments in the principles, modification and application prospects of functionalized ethosomes for topical delivery. Curr Drug Deliv. 2021;18(5):570-582.
  103. Dave V, Kumar D, Lewis S, Paliwal S. Ethosome for enhanced transdermal drug delivery of aceclofenac. Int J Drug Deliv. 2010;2(1):81-92.
  104. Chauhan N, Vasava P, Khan SL, Siddiqui FA, Islam F, Chopra H, Emran TB. Ethosomes: A novel drug carrier. J Pharm Care Health Syst. 2022; 9(3):1-7.
  105. Mahajan K, Nagpal M, Kaushik D, Vohra P. Ethosomes as a carrier for transdermal drug delivery system. J Liposome Res. 2024; 34(1):18-29.

 

Nanomedicine Journal
Volume 13, Issue 1
January 2026
Pages 54-71

Files

Share

How to cite

Statistics