Download PDF
Drug Res (Stuttg) 2021; 71(02): 54-61
DOI: 10.1055/a-1286-5750
Review

Soft Malleable Vesicles: versatile carriers for efficient topical delivery of fungal therapeutics

Preeti Gupta
1   Faculty of Pharmacy, Integral University, Lucknow
2   Kamla Nehru Institute of Management and Technology (Faculty of Pharmacy), Sultanpur
,
Antesh Kumar Jha
2   Kamla Nehru Institute of Management and Technology (Faculty of Pharmacy), Sultanpur
,
Mahesh Prasad
2   Kamla Nehru Institute of Management and Technology (Faculty of Pharmacy), Sultanpur
,
Poonam Kushwaha 
1   Faculty of Pharmacy, Integral University, Lucknow
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Fungal infections have become a subject of great concern and the incidence of fungal infections is increasing, presenting an enormous challenge to healthcare professionals. Since most of the fungal infections are occurring over the skin, the treatment option of these infections always involves topical application. However, in topical delivery drug reaches into systemic circulation through different barriers of skin. Nevertheless, due to the low permeability, skin restricts the movement of many drugs. Hence, a delivery system is required, which deliver the medicament into the skin layers or through the skin and into the systemic circulation. Ethosomes or Soft malleable vesicles are the novel lipid vesicular carrier that offer improved skin permeability and efficient delivery due to their structure and composition. They contain high concentration of ethanol, which increases the fluidity of the skin. Therefore, in the present paper, we have explored the utility of ethosomal systems in the topical treatment of fungal infections. Structure, compositions types, mechanism and techniques of preparation of ethosome also discussed in the paper.

Key words

Ethosome - fungal infection - topical drug delivery - penetration mechanism - methods of preparation - application in fungal therapeutics.


Publication History

Received: 14 August 2020

Accepted: 01 October 2020

Article published online:
02 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 VVishal P. Emerging trends in topical antifungal therapy: A review. Inventi Rapid NDDS 2015; 1-5
    PubMedSearch in Google Scholar
  • 2 Kaur IP, Kakkar S. Topical delivery of antifungal agents. Expert Opin Drug Delivery 2010; 7: 1303-1327
    CrossrefPubMedSearch in Google Scholar
  • 3 Dhamoon RK, Popli H, Gupta M. Novel drug delivery strategies for the treatment of onychomycosis. Pharm Nanotechnol 2019; 7: 24-38
    CrossrefPubMedSearch in Google Scholar
  • 4 Jaiswal PK, Kesharwani S, Kesharwani R. et al. Ethosomes: A new technology used as topical and transdermal delivery system. Journal of Drug Delivery and Therapeutics 2016; 6: 7-17
    CrossrefPubMedSearch in Google Scholar
  • 5 Tyagi LK, Kumar S, Maurya SS. et al. Ethosomes: Novel vesicular carrier for enhanced transdermal drug delivery system. Bulletin of Pharmaceutical Research 2013; 3: 6-13
    PubMedSearch in Google Scholar
  • 6 Verma S, Utrej P. Vesicular nanocarrier based treatment of skin fungal infections: Potential and emerging trends in nanoscale pharmacotherapy. Asian J Pharm Sci 2019; 14: 117-129
    CrossrefPubMedSearch in Google Scholar
  • 7 Abdulbaqi I, Darwis Y, Abdul Karim KN. et al. Ethosomal nanocarriers: The impact of constituents and formulation techniques on ethosomal properties. In Vivo Studies, and Clinical Trials. 2016; 11: 2279-2304
    PubMedSearch in Google Scholar
  • 8 Touitou E, Godin B, Dayan N. et al. Intracellular delivery mediated by an ethosomal carrier. Biomaterials 2001; 22: 3053-3059
    CrossrefPubMedSearch in Google Scholar
  • 9 Gangwar S, Singh S, Garg G. Ethosomes: A novel tool for drug delivery through the skin. Journal of Pharmacy Research 2010; 3: 688-691
    PubMedSearch in Google Scholar
  • 10 Jain H, Patel J, Joshi K. et al. Ethosomes: A novel drug carrier. International Journal of Clinical Practice 2011; 71-74
    PubMedSearch in Google Scholar
  • 11 Upadhyay N, Mandal S, Bhatia L. et al. A review on ethosomes: An emerging approach for drug delivery through the Skin. Recent Research in Science and Technology 2011; 3: 19-24
    PubMedSearch in Google Scholar
  • 12 Razavi H, Janfaza S. Ethosome: A nanocarrier for transdermal drug delivery. Journal of Paramedical Sciences 2015; 6: 38-43
    PubMedSearch in Google Scholar
  • 13 Sivakranth M, Anjuma AP, Krishnaveni C. et al. Ethosomes: A novel vesicular drug delivery System. International Journal of Advances in Pharmaceutical Research 2012; 2: 16-27
    PubMedSearch in Google Scholar
  • 14 Dhurve R, Kashyap N, Mishra A. et al. A holistic review on ethosome: A promising drug delivery system for topical fungal disease International Journal of Pharmaceutical & Biological Archives 2014; 5: 13-26
    PubMedSearch in Google Scholar
  • 15 Veintramuthu S, Santhanam R, Karthik S. Ethosomes: An exciting and promising alcoholic carrier system for treating androgenic alopecia. IntechOpen 79807 2018; 114-125
    PubMedSearch in Google Scholar
  • 16 Ainbinder D, Paolino D, Fresta M. et al. Drug delivery applications with ethosomes. Journal of Biomedical Nanotechnology 2010; 6: 558-568
    CrossrefPubMedSearch in Google Scholar
  • 17 Zhang Z, Wo Y, Zhang Y. In vitro study of ethosome penetration in human skin and hypertrophic scar tissue. Nanomedicine 2012; 8: 1026-1033
    CrossrefPubMedSearch in Google Scholar
  • 18 Mishra D, Mishra PK, Dabadghao S. et al. Comparative evaluation of hepatitis B surface antigen-loaded elastic liposomes and ethosomes for human dendritic cell uptake and immune response. Nanomedicine 2010; 6: 110-118
    CrossrefPubMedSearch in Google Scholar
  • 19 Zhou Y, Wei Y, Liu H. et al. Preparation and in vitro evaluation of ethosomal total alkaloids of sophora alopecuroides loaded by a transmembrane pH-gradient method. AAPS Pharm Sci Tech 2010; 11: 1350-1358
    CrossrefPubMedSearch in Google Scholar
  • 20 Zhang JP, Wei YH, Zhou Y. et al. Ethosomes, binary ethosomes and transfersomes of terbinafine hydrochloride: A comparative study. Arch Pharm Res 2012; 35: 109-117
    CrossrefPubMedSearch in Google Scholar
  • 21 Akhtar N, Pathak K. Cavamax W7 composite ethosomal gel of clotrimazole for improved topical delivery: Development and comparison with ethosomal gel. AAPS PharmSciTech 2012; 13: 344-355
    CrossrefPubMedSearch in Google Scholar
  • 22 Dave V, Kumar D, Lewis S. et al. Ethosome for enhanced transdermal drug delivery of aceclofenac. Int J Drug Deliv 2010; 2: 81-92
    CrossrefPubMedSearch in Google Scholar
  • 23 Song CK, Balakrishnan P, Shim CK. et al. 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
    CrossrefPubMedSearch in Google Scholar
  • 24 Ainbinder D, Touitou E. A new approach for skin tumor treatment: From delivery system characterization to in vivo evaluation. Drug Deliv Transl Res 2011; 1: 53-65
    CrossrefPubMedSearch in Google Scholar
  • 25 Bragagni M, Mennini N, Maestrelli F. et al. Comparative study of liposomes, transfersomes and ethosomes as carriers for improving topical delivery of celecoxib. Drug Deliv 2012; 19: 354-361
    CrossrefPubMedSearch in Google Scholar
  • 26 Meng S, Chen Z, Yang L. Enhanced transdermal bioavailability of testosterone propionate via surfactant-modified ethosomes. Int J Nanomedicine 2013; 8: 3051-3060
    CrossrefPubMedSearch in Google Scholar
  • 27 Chen M, Gupta V, Anselmo AC. et al. Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers. J Control Release 2014; 173: 67-74
    CrossrefPubMedSearch in Google Scholar
  • 28 Touitou E, Dayan N, Bergelson L. et al. Ethosomes- Novel vesicular carriers for enhanced delivery: Characterization and skin penetration properties. Journal of Controlled Release 2000; 65: 403-418
    CrossrefPubMedSearch in Google Scholar
  • 29 Yadav KK, Verma NK. Formulation and evaluation of ethosome of mefenamic acid using hot method. Journal of Chemical and Pharmaceutical Research 2018; 10: 4-15
    PubMedSearch in Google Scholar
  • 30 Pandey V, Golhani D, Shukla R. Ethosomes: Versatile vesicular carriers for efficient transdermal delivery of therapeutic agents. Drug Delivery 2015; 22: 988-1002
    CrossrefPubMedSearch in Google Scholar
  • 31 Dubey V, Mishra D, Dutta T. et al. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. Journal of Controlled Release 2007; 123: 148-154
    CrossrefPubMedSearch in Google Scholar
  • 32 Dubey V, Mishra D, Jain NK. Melatonin loaded ethanolic liposomes: Physicochemical characterization and enhanced transdermal delivery. European Journal of Pharmaceutics and Biopharmaceutics 2007; 67: 398-405
    CrossrefPubMedSearch in Google Scholar
  • 33 Ghule AR, Shinkar DM, Saudagar RB. et al. Ethosomes: Carrier for enhanced transdermal drug delivery system. Journal of Advanced Pharmacy Education & Research 2014; 4: 380
    PubMedSearch in Google Scholar
  • 34 Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: Ethosomes vs liposomes. Biomaterials 2000; 21: 1879-1885
    CrossrefPubMedSearch in Google Scholar
  • 35 Godin B, Touitou E. Erythromycin ethosomal systems: physicochemical characterization and enhanced antibacterial activity. Curr Drug Deliv 2005; 2: 269-275
    CrossrefPubMedSearch in Google Scholar
  • 36 Nikalje AP, Tiwari S. Ethosomes: A novel tool for transdermal drug delivery. IJRPS 2012; 2: 1-20
    PubMedSearch in Google Scholar
  • 37 Touitou E “Composition of applying active substance to or through the skin”, US Patent: 5716638, 1996
  • 38 Touitou E “Composition of applying active substance to or through the skin”, US Patent: 5540934, 1998
  • 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: 368-375
    Search in Google Scholar
  • 40 Sheer A, Chauhan M. Ethosomes as vesicular carrier for enhanced transdermal delivery of Ketoconazole - Formulation and Evaluation. J Pharma Cos 2011; 1: 1-14
    PubMedSearch in Google Scholar
  • 41 Rahul GS. Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: A comparative assessment. Saudi Pharm J 2012; 20: 161-170
    CrossrefPubMedSearch in Google Scholar
  • 42 Sarat CC. Comparative evaluation of sonicated and un-sonicated ethosomes containing Ketoconazole. Int J Advan Pharm Bio Chem 2012; 1: 15-20
    PubMedSearch in Google Scholar
  • 43 Verma P, Pathak K. Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomedicine 2012; 8: 489-496
    CrossrefPubMedSearch in Google Scholar
  • 44 Toll R, Jacobi U, Richter H. et al. Penetration profile of microspheres in follicular targeting of terminal hair follicles. Journal of Investigative Dermatology 2004; 123: 168-176
    CrossrefPubMedSearch in Google Scholar
  • 45 Aggarwal N, Goindi S. Dermatopharmacokinetic and pharmacodynamic evaluation of ethosomes of griseofulvin designed for dermal delivery. J Nanopart Res 2013; 15: 1-15
    CrossrefPubMedSearch in Google Scholar
  • 46 Zhang YT. Comparison of ethosome and liposome for skin delivery of psoralen for psoriasis therapy. International Journal of pharmaceutics 2014; 1-4
    PubMedSearch in Google Scholar
  • 47 Guo F, Wang J, Ma M. et al. Skin targeted lipid vesicles as novel nano-carrier of ketoconazole: characterization, in vitro and in vivo evaluation. J Mater Sci Mater Med 2015; 26: 1-13
    PubMedSearch in Google Scholar
  • 48 Indora N, Kaushik D. Design, development and evaluation of ethosomal gel of fluconazole for topical fungal infection. International Journal of Engineering Science Invention Research & Development 2015; 1: 280-306
    PubMedSearch in Google Scholar
  • 49 Rathore GS, Tanwar YS, Naruka PS. Comparative evaluation of in -vitro antifungal activity of ethosomal and liposome gel formulated with fluconazole for treatment of deep fungal skin infections. Pharmaceutical Education and Research 2015; 4: 60-66
    PubMedSearch in Google Scholar
  • 50 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; 6: 45-49
    PubMedSearch in Google Scholar
  • 51 Kumar AC, Krishna RG, Venkanna CK. et al. Formulation and characterization of itraconazole ethosomal gel for topical application. J Bio Innov 2017; 6: 55-64
    PubMedSearch in Google Scholar
  • 52 Faisal W, Soliman GM, Hamdan AM. Enhanced skin deposition and delivery of voriconazole using ethosomal preparations. J Liposome Res 2018; 28: 14-21
    CrossrefPubMedSearch in Google Scholar
  • 53 Behtash AO, Nasrollahi SA, Nafisia S. Design, synthesis of novel vesicular systems using turpentine as a skin permeation enhancer. Journal of Drug Delivery Science and Technology 2018; 43: 327-332
    CrossrefPubMedSearch in Google Scholar
  • 54 Khan WA, Sharma V, Maurya P. et al. Development and characterization of the oxiconazole nitrate loaded ethosomal gel for treating fungal infections. World Journal of Pharmaceutical Research 2019; 8: 134-136
    PubMedSearch in Google Scholar
  • 55 Zhang L, Li X, Zhu S. et al. Dermal targeting delivery of terbinafine hydrochloride using novel multi-ethosomes: A new approach to fungal infection treatment. Coatings 2020; 10: 304
    CrossrefPubMedSearch in Google Scholar
  • 56 Nayak D, Tawale RM, Aranjani JM. et al. Formulation, optimization and evaluation of novel ultra-deformable vesicular drug delivery system for an anti-fungal drug. AAPS Pharm Sci Tech 2020; 21: 140
    CrossrefPubMedSearch in Google Scholar
  • 57 Abdulbaqi IM, Darwis Y, Khan NA. et al. Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials. International Journal of Nanomedicine 2016; 11: 2279-2304
    CrossrefPubMedSearch in Google Scholar
  • 58 Zahid SR, Upmanyu N, Dangi S. et al. Ethosome: a novel vesicular carrier for transdermal drug delivery. Journal of Drug Delivery & Therapeutics 2018; 8: 318-326
    CrossrefPubMedSearch in Google Scholar