NOVEL APPROACHES IN ETHOSOMAL DRUG DELIVERY: APPLICATION IN DERMATOLOGY AND BEYOND

SIMRAN NEGI; SHALU VERMA; PRAYAG RAJ; ALKA SINGH

doi:10.22159/ijap.2025v17i5.54400

Authors

SIMRAN NEGI Department of Pharmaceutics, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Prem Nagar, Dehradun-248007, India
SHALU VERMA Department of Pharmaceutics, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Prem Nagar, Dehradun-248007, India
PRAYAG RAJ Department of Pharmaceutics, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Prem Nagar, Dehradun-248007, India
ALKA SINGH School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Balawala, Dehradun, Uttarakhand-248007, India https://orcid.org/0000-0002-9387-2160

DOI:

https://doi.org/10.22159/ijap.2025v17i5.54400

Keywords:

Ethosomes, Skin, Applications, Transdermal, Bioavailability

Abstract

Skin is a complex and dynamic structure with multiple layers, and it is the body's largest organ. It is the protective barrier between the external and internal environment; it comprises three layers (epidermis, dermis, and hypodermis). The skin performs various vital functions in the body. A conventional drug delivery system (CDDS) is the method of administering drugs into the body through oral, parenteral, and topical administration. This delivery system has several drawbacks, including low bioavailability, uncontrolled release, and poor solubility. A novel carrier and TDDS (Transdermal Drug Delivery) systems were introduced to overcome these drawbacks. It is an advanced drug delivery system designed to overcome the drawbacks of conventional methods and improve therapeutic outcomes. Some examples of novel and transdermal carriers are liposomes, niosomes, ethosomes, and microspheres. Ethosomes are preferred over liposomes and niosomes due to their high ethanol content, which enhances skin penetration and allows deeper drug delivery. TDDS delivers drugs into the deeper layer of the skin and provides a therapeutic effect by avoiding first-pass metabolism. They are generally used to treat various diseases. Ethosomes are highly advanced lipid-based nano-carriers designed to improve transdermal and dermal drug delivery systems. The main aim of writing this review paper is to summarize the focus on the key aspects, such as types of ethosomes, the mechanism of action of ethosomes, the method of preparation, composition, application, characterization, the patent, marketed formulation, and factors of ethosomes.

References

1. Haftek M, Abdayem R, Guyonnet Debersac P. Skin minerals: key roles of inorganic elements in skin physiological functions. Int J Mol Sci. 2022;23(11):6267. doi: 10.3390/ijms23116267, PMID 35682946.

2. Gilaberte Y, Prieto Torres L, Pastushenko I, Juarranz A. Anatomy and function of the skin. In: Nanoscience in dermatology. Amsterdam: Elsevier; 2016 Jan 1. p. 1-14. doi: 10.1016/B978-0-12-802926-8.00001-X.

3. Bouwstra JA, Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta. 2006 Dec 1;1758(12):2080-95. doi: 10.1016/j.bbamem.2006.06.021, PMID 16945325.

4. Kumar V, Praveen N, Kewlani P, Arvind, Singh A, Gautam AK. Transdermal drug delivery systems. In: Santra TS, Shinde AU, editors. Advanced drug delivery. Singapore: Springer Nature Singapore; 2023. p. 333-62. doi: 10.1007/978-981-99-6564-9_13.

5. Alenzi AM, Albalawi SA, Alghamdi SG, Albalawi RF, Albalawi HS, Qushawy M. Review on different vesicular drug delivery systems (VDDSs) and their applications. Recent Pat Nanotechnol. 2023;17(1):18-32. doi: 10.2174/1872210516666220228150624, PMID 35227188.

6. Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry. Adv Colloid Interface Sci. 1995 Jun 27;58(1):1-55. doi: 10.1016/0001-8686(95)00242-I.

7. Das SK, Chakraborty S, Roy C, Rajabalaya R, Mohaimin AW, Khanam J. Ethosomes as novel vesicular carrier: an overview of the principle preparation and its applications. Curr Drug Deliv. 2018 Jan 16;15(6):795-817. doi: 10.2174/1567201815666180116091604, PMID 29336262.

8. Mbah CC, Builders PF, Attama AA. Nanovesicular carriers as alternative drug delivery systems: ethosomes in focus. Expert Opin Drug Deliv. 2014;11(1):45-59. doi: 10.1517/17425247.2013.860130, PMID 24294974.

9. 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 Apr 3;65(3):403-18. doi: 10.1016/s0168-3659(99)00222-9, PMID 10699298.

10. Mbah CC, Builders PF, Attama AA. Nanovesicular carriers as alternative drug delivery systems: ethosomes in focus. Expert Opin Drug Deliv. 2014;11(1):45-59. doi: 10.1517/17425247.2013.860130, PMID 24294974.

11. Mohanty D, Mounika A, Bakshi V, Akiful Haque M, Keshari Sahoo C. Ethosomes: a novel approach for transdermal drug delivery. IJCTR. 2018;11(8):219-26. doi: 10.20902/IJCTR.2018.110826.

12. Verma P, Pathak K. Therapeutic and cosmeceutical potential of ethosomes: an overview. J Adv Pharm Technol Res. 2010;1(3):274-82. doi: 10.4103/0110-5558.72415.

13. Colaco HA, Mestre B, Pela DCO T, Doutora P, Beco AC, Reis P, Auxiliar P, Pela C, Manuela De Jesus M, Gaspar G, Auxiliar I. Development of ethosomes as skin carriers for Sambucus nigra l. extracts. Universidade de Lisboa Faculdade de Farmacia; 2021.

14. Chauhan AS, Chand P, Parashar T. Lipid-based nanoparticles: strategy for targeted cancer therapy. BIO Integr. 2025;6(1). doi: 10.15212/bioi-2024-0107.

15. Mohammed MI, Makky AM, Abdellatif MM. Formulation and characterization of ethosomes bearing vancomycin hydrochloride for transdermal delivery. Int J Pharm Pharm Sci. 2014 Nov 1;6(11):190-4.

16. Alfawaz Altamimi AS, Arockia Babu M, Afzal M, Bishoyi AK, Roopashree R, Saini S. Exosomes derived from natural killer cells: transforming immunotherapy for aggressive breast cancer. Med Oncol. 2025;42(4):114. doi: 10.1007/s12032-025-02647-y, PMID 40100465.

17. Musielak E, Krajka Kuzniak V. Liposomes and ethosomes: comparative potential in enhancing skin permeability for therapeutic and cosmetic applications. Cosmetics. 2024;11(6):191. doi: 10.3390/cosmetics11060191.

18. Fadaei MS, Fadaei MR, Kheirieh AE, Rahmanian Devin P, Dabbaghi MM, Nazari Tavallaei K. Niosome as a promising tool for increasing the effectiveness of anti-inflammatory compounds. Excli J. 2024 Feb 7;23:212-63. doi: 10.17179/excli2023-6868, PMID 38487088.

19. Satyam G, Shivani S, Garima G. Ethosomes: a novel tool for drug delivery through the skin. J Pharm Res. 2010;3(4):688-91.

20. Opatha SA, Titapiwatanakun V, Chutoprapat R. Transfersomes: a promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics. 2020;12(9):855. doi: 10.3390/pharmaceutics12090855, PMID 32916782.

21. Gupta R, Badhe Y, Rai B, Mitragotri S. Molecular mechanism of the skin permeation enhancing effect of ethanol: a molecular dynamics study. RSC Adv. 2020 Mar 24;10(21):12234-48. doi: 10.1039/d0ra01692f, PMID 35497613.

22. Ghosh A, Sirisolla JD. Ethosomes: design, composition and characterization in different disease management. YMER. 2024;23(9):1173-84.

23. Paiva Santos AC, Silva AL, Guerra C, Peixoto D, Pereira Silva M, Zeinali M. Ethosomes as nanocarriers for the development of skin delivery formulations. Pharm Res. 2021 May 25;38(6):947-70. doi: 10.1007/s11095-021-03053-5, PMID 34036520.

24. Ruwizhi N, Aderibigbe BA. The efficacy of cholesterol-based carriers in drug delivery. Molecules 2020;25(18):4330.

25. Mast R. Glycerine in creams lotions and hair care products. In: Jungermann E, Sonntag NO, editors. Glycerine. Boca Raton: CRC Press; 2018. p. 345-79. doi: 10.1201/9780203753071-13.

26. Richard C, Souloumiac E, Jestin J, Blanzat M, Cassel S. Influence of dermal formulation additives on the physicochemical characteristics of catanionic vesicles. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2018 Dec 5;558:373-83. doi: 10.1016/j.colsurfa.2018.09.007.

27. Chauhan N, Vasava P, Khan SL, Siddiqui FA, Islam F, Chopra H. Ethosomes: a novel drug carrier. Ann Med Surg (Lond). 2022 Oct 1;82:104595. doi: 10.1016/j.amsu.2022.104595, PMID 36124209.

28. Neeraj Kumar, Anubhav Dubey, Ashish Mishra Pallavi Tiwari. Ethosomes: a novel approach in transdermal drug delivery system. International Journal of Pharmacy & Life Sciences. 2020;11(5):6598-607.

29. Dhurke R, Pravalika G, Chandhana P, Chiranjitha I. Minoxidil ethosomes for treatment of alopecia. International Journal of Recent Scientific Research. 2020;11(1):37112-7. doi: 10.24327/ijrsr.2020.1101.5056.

30. Parmar P, Mishra A, Pathak A. Preparation and evaluation of ethosomal gel of clotrimazole for fungal infection by mechanical dispersion method. Current Research in Pharmaceutical Sciences. 2016 Jul 9;6(2):45-9.

31. Zhou Y, Wei YH, Zhang GQ, Wu XA. Synergistic penetration of ethosomes and lipophilic prodrug on the transdermal delivery of acyclovir. Arch Pharm Res. 2010;33(4):567-74. doi: 10.1007/s12272-010-0411-2, PMID 20422366.

32. Seyedehhamideh Razavi, Alireza Partoazar, Nasrin Takzaree. Silver sulfadiazine nanoethogel for burn healing: characterization and investigation of its in vivo effects. Nanomedicine. 2018 Jun;13(11):1319–31. doi: 10.2217/nnm-2017-0385.

33. Peram MR, Jalalpure S, Kumbar V, Patil S, Joshi S, Bhat K. Factorial design-based curcumin ethosomal nanocarriers for the skin cancer delivery: in vitro evaluation. J Liposome Res. 2019;29(3):291-311. doi: 10.1080/08982104.2018.1556292, PMID 30526186.

34. Nasri S, Ebrahimi Hosseinzadeh B, Rahaie M, Hatamian Zarmi A, Sahraeian R. Thymoquinone-loaded ethosome with breast cancer potential: optimization in vitro and biological assessment. J Nanostructure Chem. 2020;10(1):19-31. doi: 10.1007/s40097-019-00325-w.

35. Ahmed TA, Alzahrani MM, Sirwi A, Alhakamy NA. The antifungal and ocular permeation of ketoconazole from ophthalmic formulations containing trans-ethosomes nanoparticles. Pharmaceutics. 2021;13(2):151. doi: 10.3390/pharmaceutics13020151, PMID 33498849.

36. Abd El Alim SH, 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. doi: 10.1016/j.ijpharm.2019.04.001, PMID 30951860.

37. Fathalla D, Youssef EM, 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. doi: 10.3390/pharmaceutics12050446, PMID 32403379.

38. Yu Z, LV H, Han G, Ma K. Ethosomes loaded with cryptotanshinone for acne treatment through topical gel formulation. PLOS One. 2016;11(7):e0159967. doi: 10.1371/journal.pone.0159967, PMID 27441661.

39. Tarek M Ibrahim, Marwa H Abdallah, Nagia A El Megrab, Hanan M El Nahas. Transdermal ethosomal gel nanocarriers; a promising strategy for enhancement of the anti-hypertensive effect of carvedilol. Journal of Liposome Research. 2019 Sep;29(3):215-28. doi: 10.1080/08982104.2018.1529793.

40. Paiva Santos AC, Silva AL, Guerra C, Peixoto D, Pereira Silva M, Zeinali M. Ethosomes as nanocarriers for the development of skin delivery formulations. Pharm Res. 2021 May 25;38(6):947-70. doi: 10.1007/s11095-021-03053-5, PMID 34036520.

41. Wang Y, Song J, Zhang F, Zeng K, Zhu X. Antifungal photodynamic activity of hexyl-aminolevulinate ethosomes against Candida albicans biofilm. Front Microbiol. 2020 Sep 11;11:2052. doi: 10.3389/fmicb.2020.02052, PMID 33042036.

42. Goindi S, Dhatt B, Kaur A. Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies. J Microencapsul. 2014 Nov 1;31(7):716-24. doi: 10.3109/02652048.2014.918667, PMID 24963956.

43. Verma P, Pathak K. Therapeutic and cosmeceutical potential of ethosomes: an overview. J Adv Pharm Technol Res. 2010;1(3):274-82. doi: 10.4103/0110-5558.72415, PMID 22247858.

44. Akhtar N, Akhtar N. Development of stable tocopherol succinate-loaded ethosomes to enhance transdermal permeation: in vitro and in vivo characterizations. J Cosmet Dermatol. 2022 Oct 1;21(10):4942-55. doi: 10.1111/jocd.14907, PMID 35274433.

45. Omidian H, Wilson RL, Chowdhury SD. Enhancing therapeutic efficacy of curcumin: advances in delivery systems and clinical applications. Gels. 2023 Aug 1;9(8):596. doi: 10.3390/gels9080596, PMID 37623051.

46. Pathan IB, Jaware BP, Shelke S, Ambekar W. Curcumin-loaded ethosomes for transdermal application: formulation optimization in vitro and in vivo study. J Drug Deliv Sci Technol. 2018 Apr 1;44:49-57. doi: 10.1016/j.jddst.2017.11.005.

47. Rezapour E, Kariminezhad H, Mostafazadeh A, Ghasemi R, Pourbagher R, Neyshaburi EZ. Enhancement of transdermal vaccination using electrothermal active interfaces. J Drug Deliv Sci Technol. 2024 Jun 1;96:105639. doi: 10.1016/j.jddst.2024.105639.

48. Pawar S, Shivarkar R, Dhole S. Ethosome: a novel carrier used in transdermal and topical drug delivery. International Journal of Pharmaceutical Research and Applications. 2024 May-Jun;9(3):2442-52. doi: 10.35629/4494-090324422452.

49. Abdallah HM, El Megrab NA, Balata GF, Eissa NG. Niosomal and ethosomal gels: a comparative in vitro and ex vivo evaluation for repurposing of spironolactone. J Drug Deliv Sci Technol. 2022 Aug 1;74:103583. doi: 10.1016/j.jddst.2022.103583.

50. Claudia Paiva Santos A, Gama M, Peixoto D, Sousa Oliveira I, Ferreira Faria I, Zeinali M. Nanocarrier based dermopharmaceutical formulations for the topical management of atopic dermatitis. Int J Pharm. 2022 Apr 25;618:121656. doi: 10.1016/j.ijpharm.2022.121656, PMID 35278601.

51. Ferreira L, Mascarenhas Melo F, Rabaca S, Mathur A, Sharma A, Giram PS. Cyclodextrin-based dermatological formulations: dermopharmaceutical and cosmetic applications. Colloids Surf B Biointerfaces. 2023 Jan 1;221:113012. doi: 10.1016/j.colsurfb.2022.113012, PMID 36395617.

52. Diclofenac topical: uses side effects, interactions, pictures, warnings and dosing-webmd. Available from: https://www.webmd.com/drugs/2/drug-22221-1065/diclofenac-sodiumtopical/diclofenac-1-topical/details. [Last accessed on 22 Mar 2025].

53. Buy dermovate cream and ointment online. Next-day delivery UK. Available from: https://www.cloudpharmacy.co.uk/online-doctor/eczema-psoriasis/dermovate-cream-ointment. [Last accessed on 22 Mar 2025].

54. Ketoconazole Bp 2.0% W/w Cream (kt-sal Cream). Available from: https://www.indiamart.vol.20gat₹130/pieceinsurat.com./proddetail/ketoconazole-bp-2-0-w-w-cream-kt-sal-cream-2851103006148.html?srsltid=afmbooqoojb5qnuvomz-gmbwcwy2oastkiof1ooaciijrpgbi1pzdkth. [Last accessed on 22 Mar 2025].

55. Kimbonguila A, Matos L, Petit J, Scher J, Nzikou JM. Effect of physical treatment on the physicochemical, rheological and functional properties of yam meal of the cultivar ngumvu from Dioscorea alata L. of Congo. Int J Recent Sci Res. 2019;10(11):30693-5.

56. Clonazepam (Klonopin): uses side effects, interactions pictures, warnings and dosing-WebMD. Available from: https://www.webmd.Com/drugs/2/drug-920-6006/klonopin-oral/clonazepam-oral/details. [Last accessed on 22 Mar 2025].

57. Anuradha BR, Bai YD, Sailaja S, Sudhakar J, Priyanka M, Deepika V. Evaluation of anti-inflammatory effects of curcumin gel as an adjunct to scaling and root planing: a clinical study. J Int Oral Health. 2015 Jul;7(7):90-3. PMID 26229378.

58. Google Patents. Available from: https://patents.google.com. [Last accessed on 5 May 2025].