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Abstract

Transdermal drug delivery systems (TDDS) provide an effective route for administering therapeutic agents through the skin into systemic circulation, offering advantages such as improved patient compliance, avoidance of first pass metabolism, and sustained drug release. However, the major challenge limiting their efficiency is the skin’s outermost layer, the stratum corneum, which acts as a strong barrier to drug permeation. Conventional formulations often fail to achieve sufficient bioavailability for many drugs, particularly hydrophilic and large molecular weight compounds. In recent years, vesicular drug delivery systems have gained prominence as advanced carriers for enhancing skin permeation. Among these, ethosomes have emerged as a promising nanocarrier system due to their soft, flexible vesicular structure composed of phospholipids, ethanol, and water. Ethosomes are distinguished by their high ethanol content, which imparts malleability to vesicles and disrupts lipid packing in the stratum corneum, leading to increased drug permeation and deposition within deeper skin layers.The unique composition and mechanism of ethosomes allow for the efficient delivery of both hydrophilic and lipophilic drugs, improving therapeutic efficacy while minimizing side effects. This review critically discusses the design aspects, formulation parameters, and mechanisms underlying ethosomal skin permeation. It also explores the broad therapeutic applications of ethosomes, emphasizing their superiority over conventional transdermal systems. Overall, ethosomes represent a breakthrough in nanocarrier-mediated transdermal delivery, paving the way for more effective, patient-friendly therapeutic approaches.

Keywords

Ethosomes, Transdermal drug delivery, Skin permeation, Vesicular carriers, Nanotechnology, Formulation optimization, Therapeutic efficacy

Introduction

Transdermal drug delivery systems (TDDS) have evolved as a novel and non-invasive route for systemic drug administration, offering several benefits over traditional oral or parenteral drug delivery. These systems enable the controlled release of drugs through the skin, ensuring steady plasma concentrations and improved patient adherence to treatment regimens (1). TDDS bypass the hepatic first pass effect and minimize gastrointestinal degradation, making them ideal for drugs with poor oral bioavailability or short half-lives (2). Despite these advantages, conventional transdermal carriers such as ointments, gels, and patches face major limitations due to the highly selective permeability of the stratum corneum. This outermost skin layer, rich in keratinized cells and lipids, restricts the penetration of most therapeutic agents, especially those with high molecular weight or hydrophilic characteristics (3). To address these limitations, researchers have explored various enhancement techniques, including chemical penetration enhancers, iontophoresis, and the use of vesicular systems. Vesicular drug delivery systems such as liposomes, niosomes, and transfersomes have emerged as promising platforms for improving drug solubility, stability, and penetration through the skin (4). These carriers can encapsulate both hydrophilic and lipophilic drugs and modulate release kinetics. Among them, ethosomes have attracted considerable interest for their exceptional skin permeability and stability. Ethosomes are soft, malleable lipid vesicles composed primarily of phospholipids, ethanol, and water (5). The incorporation of ethanol confers elasticity and fluidity to the vesicles while simultaneously enhancing skin permeability by disrupting the lipid organization within the stratum corneum (6). This unique combination allows ethosomes to traverse the skin barrier efficiently and deposit drugs into deeper layers, achieving both localized and systemic effects. The significance of ethosomes lies in their ability to overcome the shortcomings of conventional transdermal carriers and deliver a broad spectrum of drugs, including peptides, hormones, antivirals, and anti-inflammatory agents (7). Their non-invasive nature, high entrapment efficiency, and controlled drug release profile have positioned them as a superior alternative for transdermal drug delivery. The objective of this review is to provide a comprehensive discussion on ethosomes as advanced transdermal carriers. It explores their structural design, formulation parameters, mechanisms of skin permeation, and therapeutic applications. Additionally, it critically evaluates their clinical relevance and future potential in enhancing the efficacy and safety of transdermal drug delivery systems.

Reference

  1. Almuqbil RM, Aldhubiab BE. Ethosome-based transdermal drug delivery: its structural components, preparation techniques, and therapeutic applications across metabolic, chronic, and oncological conditions. Pharmaceutics. 2025; 17:1–15.
  2. Waqar MA, Zaman M, Hameed H, Munir M. Ethosomes: a novel approach for the delivery of drug. Int J Pharm Integr Health Sci. 2023;4(2):1–12.
  3. Devaki J, Pavuluri S, Suma N. Ethosomes: a vesicular carrier as a novel tool for transdermal drug delivery system. J Drug Deliv Ther. 2023;13(4):45–53.
  4. Azzahra L, Mita S, Sriwidodo S. Formulation, characterization, and herbal drug delivery applications of ethosome, transfersome, and transethosome. Indones J Pharm Sci. 2020;2(3):120–130.
  5. Mohapatra S, Mirza MA, Ahmad S, Farooq U, Ansari MJ, Kohli K, et al. Quality by design assisted optimization and risk assessment of black cohosh loaded ethosomal gel for menopause. Pharmaceutics. 2023;15(2):1–15.
  6. 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.
  7. Bhalaria MK, Naik S, Misra AN. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases. Indian J Exp Biol. 2009;47(5):368–375.
  8. Natsheh H, Touitou E. Phospholipid vesicles for dermal/transdermal and nasal administration of active molecules: effect of surfactants and alcohols on lipid bilayer fluidity and penetration enhancement. Molecules. 2020; 25:2959.
  9. Narasapuram S, Peram DR, Dugasani S. Ethosomes—an innovative method for drug delivery systems. Future J Pharm Health Sci. 2025;5(2).
  10. Devaki J, Pavuluri S, Suma N. Ethosomes: a vesicular carrier as a novel tool for transdermal drug delivery system. J Drug Deliv Ther. 2023;13(4).
  11. Rosmiati M, Wulantresna D, Emelia R. Transethosomes as vesicular drug delivery: a modified form of ethosomes and transfersomes. Ranah Res J. 2025;7(3).
  12. Chauhan N, Vasava P, Khan SL, Siddiqui F, Islam F, Chopra H, et al. Ethosomes: a novel drug carrier. Ann Med Surg. 2022; 82:104595.
  13. Shinde P, Page A, Bhattacharya S. Ethosomes and their monotonous effects on skin cancer disruption. Front Nanotechnol. 2023;5.
  14. Emanet M, Ciofani G. Ethosomes as promising transdermal delivery systems of natural-derived active compounds. Adv NanoBiomed Res. 2023;3(1).
  15. Almuqbil RM, Aldhubiab BE. Ethosome-based transdermal drug delivery: its structural components, preparation techniques, and therapeutic applications across metabolic, chronic, and oncological conditions. Pharmaceutics. 2025; 17:1–15.
  16. 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.
  17. Devaki J, Pavuluri S, Suma N. Ethosomes: a vesicular carrier as a novel tool for transdermal drug delivery system. J Drug Deliv Ther. 2023;13(4):45–53.
  18. Azzahra L, Mita S, Sriwidodo S. Formulation, characterization, and herbal drug delivery applications of ethosome, transfersome, and transethosome. Indones J Pharm Sci. 2020;2(3):120–130.
  19. Waqar MA, Zaman M, Hameed H, Munir M. Ethosomes: a novel approach for the delivery of drug. Int J Pharm Integr Health Sci. 2023;4(2):1–12.
  20. Bhalaria MK, Naik S, Misra AN. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases. Indian J Exp Biol. 2009;47(5):368–375.
  21. Mohapatra S, Mirza MA, Ahmad S, Farooq U, Ansari MJ, Kohli K, et al. Quality by design assisted optimization and risk assessment of black cohosh loaded ethosomal gel for menopause. Pharmaceutics. 2023;15(2):1–15.
  22. Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. Int J Pharm. 2006;322(1–2):60–66.
  23. Honeywell NG, El-Maghraby GM. Ethosomes as a carrier for skin delivery of drugs: mechanistic studies using confocal microscopy. Eur J Pharm Biopharm. 2008;68(3):690–699.
  24. Devaki J, Pavuluri S, Suma N. Ethosomes: a vesicular carrier as a novel tool for transdermal drug delivery system. J Drug Deliv Ther. 2023;13(4):45–53.
  25. Almuqbil RM, Aldhubiab BE. Ethosome-based transdermal drug delivery: its structural components, preparation techniques, and therapeutic applications across metabolic, chronic, and oncological conditions. Pharmaceutics. 2025; 17:1–15.
  26. Waqar MA, Zaman M, Hameed H, Munir M. Ethosomes: a novel approach for the delivery of drug. Int J Pharm Integr Health Sci. 2023;4(2):1–12.
  27. Azzahra L, Mita S, Sriwidodo S. Formulation, characterization, and herbal drug delivery applications of ethosome, transfersome, and transethosome. Indones J Pharm Sci. 2020;2(3):120–130.
  28. 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.
  29. Jain S, Umamaheshwari RB, Bhadra D, Jain NK. Ethosomes: a novel vesicular carrier for enhanced transdermal delivery of drugs. Indian J Pharm Sci. 2003;65(4):372–375.
  30. Bhalaria MK, Naik S, Misra AN. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases. Indian J Exp Biol. 2009;47(5):368–375.
  31. Mishra D, Garg M, Dubey A. Formulation and evaluation of ethosomes for transdermal delivery of antihypertensive drugs. J Pharm Invest. 2012;42(2):103–110.
  32. Gaur PK, Mishra S, Purohit S, Dave K. Ethosomes: a novel vesicular carrier for enhanced transdermal delivery of drugs. Asian J Pharm Sci. 2011;6(3):175–182.
  33. Mohapatra S, Mirza MA, Ahmad S, Farooq U, Ansari MJ, Kohli K, et al. Quality by design assisted optimization and risk assessment of black cohosh loaded ethosomal gel for menopause. Pharmaceutics. 2023;15(2):1–15.
  34. Waqar MA, Zaman M, Hameed H, Munir M. Ethosomes: a novel approach for the delivery of drug. Int J Pharm Integr Health Sci. 2023;4(2):1–12.
  35. Devaki J, Pavuluri S, Suma N. Ethosomes: a vesicular carrier as a novel tool for transdermal drug delivery system. J Drug Deliv Ther. 2023;13(4):45–53.
  36. Azzahra L, Mita S, Sriwidodo S. Formulation, characterization, and herbal drug delivery applications of ethosome, transfersome, and transethosome. Indones J Pharm Sci. 2020;2(3):120–130.
  37. Almuqbil RM, Aldhubiab BE. Ethosome-based transdermal drug delivery: its structural components, preparation techniques, and therapeutic applications across metabolic, chronic, and oncological conditions. Pharmaceutics. 2025; 17:1–15.
  38. 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.
  39. Bhalaria MK, Naik S, Misra AN. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases. Indian J Exp Biol. 2009;47(5):368–375.
  40. Mohapatra S, Mirza MA, Ahmad S, Farooq U, Ansari MJ, Kohli K, et al. Quality by design assisted optimization and risk assessment of black cohosh loaded ethosomal gel for menopause. Pharmaceutics. 2023;15(2):1–15.
  41. Mishra D, Jain S, Jain GK. Ethosomes as novel vesicular carriers for transdermal delivery of anti-inflammatory drug. Int J Pharm. 2007;334(1–2):16–22.
  42. Sharma V, Singh P, Kumar A. Development of ibuprofen-loaded ethosomal gel for transdermal application. J Pharm Invest. 2018;48(4):465–476.
  43. Bhalaria MK, Naik S, Misra AN. Ethosomes for antifungal drug delivery. Indian J Exp Biol. 2009;47(5):368–375.
  44. Jain S, Umamaheshwari RB, Bhadra D. Ethosomes for transdermal and dermal delivery of drugs. J Control Release. 2004;99(3):383–392.
  45. Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for transdermal delivery of drugs. Eur J Pharm Biopharm. 2007;66(2):220–228.
  46. Touitou E, Godin B. Ethosomes for transdermal delivery of CNS drugs. J Biomed Nanotechnol. 2008;4(4):434–442.
  47. Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of hormones. J Control Release. 2005;106(3):405–421.
  48. Verma DD, Fahr A. Ethosomes: enhanced delivery of active agents through the skin. Skin Pharmacol Physiol. 2004;17(3):101–110.
  49. Azzahra L, Mita S, Sriwidodo S. Formulation and herbal drug delivery applications of ethosomes. Indones J Pharm Sci. 2020;2(3):120–130.
  50. Zhang YT, Wang JJ, Yang G. Ethosomal systems for topical delivery of phytoconstituents. J Drug Deliv Sci Technol. 2022; 74:103565.
  51. Almuqbil RM, Aldhubiab BE. Ethosome-based transdermal drug delivery: structural components, preparation techniques, and therapeutic applications. Pharmaceutics. 2025; 17:1–15.
  52. Waqar MA, Zaman M, Hameed H, Munir M. Ethosomes: a novel approach for the delivery of drug. Int J Pharm Integr Health Sci. 2023;4(2):1–12.
  53. Bhalaria MK, Naik S, Misra AN. Ethosomes: a novel delivery system for antifungal drugs. Indian J Exp Biol. 2009;47(5):368–375.
  54. Devaki J, Pavuluri S, Suma N. Ethosomes: a vesicular carrier as a novel tool for transdermal drug delivery system. J Drug Deliv Ther. 2023;13(4):45–53.
  55. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration. J Control Release. 2000;65(3):403–418.
  56. Rai VK, Mishra N, Yadav KS, Yadav NP. Nano carriers as vesicular carriers for dermal and transdermal drug delivery. Asian J Pharm Sci. 2018;13(3):168–183.
  57. Azzahra L, Mita S, Sriwidodo S. Formulation, characterization, and herbal drug delivery applications of ethosome, transfersome, and transethosome. Indones J Pharm Sci. 2020;2(3):120–130.
  58. Das S, Suresh PK. Nanosomes in drug targeting and delivery: an overview. Int J Pharm Sci Rev Res. 2010;3(1):8–17.
  59. Sharma A, Garg T, Goyal AK, Rath G. Role of ethosomes as vesicular carriers: an overview. J Adv Pharm Technol Res. 2010;1(3):274–282.
  60. Jain S, Tiwary AK, Sapra B, Jain NK. Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS PharmSciTech. 2007;8(4):249–257.
  61. Mishra D, Mishra PK, Dubey V, Dabadghao S. Ethosomal gel of clotrimazole for improved topical delivery. Eur J Pharm Biopharm. 2008;68(3):578–586.
  62. Mohapatra S, Mirza MA, Ahmad S, Farooq U, Ansari MJ, Kohli K, et al. Quality by design assisted optimization and risk assessment of ethosomal gel. Pharmaceutics. 2023;15(2):1–15.
  63. Rai S, Pandey V, Rai G. Transfersomes as versatile and flexible nano-vesicular carriers in skin cancer therapy. Pharmaceutics. 2021;13(7):1–20.
  64. Manca ML, Cencetti C, Peris JE, Matricardi P, Fadda AM, Manconi M. Innovative transethosomes with hyaluronic acid: characterization and in vitro/in vivo studies. Eur J Pharm Biopharm. 2019; 144:79–87.
  65. US Patent 9320802B2. Ethosomal compositions for enhanced transdermal delivery. 2016.
  66. Touitou E, inventor. Ethosomal formulations for cosmetic and pharmaceutical applications. US Patent 20070116776A1. 2007.
  67. Wang W, Zhang L, Zhang X, Chen Y. Stimuli-responsive ethosomes for transdermal smart drug delivery. Adv Drug Deliv Rev. 2022; 185:114130.
  68. Wang T, Deng Y, Chen W, Zhang H. Toxicity evaluation of lipid vesicles for transdermal drug delivery. J Biomed Nanotechnol. 2021;17(8):1650–1661.
  69. Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. Int J Pharm. 2006;322(1–2):60–66.
  70. De Jong WH, Borm PJA. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine. 2008;3(2):133–149.
  71. European Medicines Agency. Reflection paper on nanotechnology-based medicinal products. EMA/CHMP/706260/2010.
  72. Mura S, Manconi M, Sinico C, Valenti D, Fadda AM. Ethosomes for topical delivery of antioxidants. Pharmaceutics. 2019;11(2):85–99.
  73. Godin B, Touitou E. Mechanism of bacitracin permeation enhancement through the skin. J Control Release. 2004;94(2–3):365–379.
  74. Xu Q, Lee JY, Wang CH. Advances in transdermal drug delivery using nanocarriers. J Control Release. 2021; 335:337–353.
  75. Kwon YJ, Lim J, Park JH. Future perspectives of smart transdermal delivery systems. Adv Drug Deliv Rev. 2023; 191:114154.

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Aishwarya Morkhade
Corresponding author

B. Pharm, Laddhad College of Pharmacy Yealgao, Buldhana, Maharashtra, India

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Sakshi Sisodiya
Co-author

B. Pharm, Laddhad College of Pharmacy Yealgao, Buldhana, Maharashtra, India

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Vishvesh Bajad
Co-author

B. Pharm, Laddhad College of Pharmacy Yealgao, Buldhana, Maharashtra, India

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M. A. Mapari
Co-author

B. Pharm, Laddhad College of Pharmacy Yealgao, Buldhana, Maharashtra, India

Aishwarya Morkhade*, Sakshi Sisodiya, Vishvesh Bajad, M. A. Mapari, Ethosomes As Advanced Transdermal Drug Carriers: A Critical Review of Design, Skin Permeation Mechanisms, Formulation Parameters, and Therapeutic Efficacy, Int. J. Sci. R. Tech., 2026, 3 (1), 215-226. https://doi.org/10.5281/zenodo.18296248

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