Beyond the Skin Barrier: How Transfersomes and Transethosomes are Revolutionizing Topical Therapies

Authors

  • Widayanti Supraba Universitas Padjadjaran
  • Patihul Husni Universitas Padjadjaran
  • Anis Yohana Chaerunisaa Universitas Padjadjaran

Keywords:

Ultra-deformable nanovesicles, transferosomes, transethosomes, topical delivery, dermatology

Abstract

Introduction: The fundamental challenge of effective skin permeation has long limited the therapeutic potential of topical drug delivery systems. Conventional formulations frequently fail to achieve adequate penetration through the skin barrier, necessitating innovative approaches to enhance drug bioavailability while maintaining targeted delivery to specific skin layers. Aims: This review evaluates the transformative impact of transfersomes and transethosomes as advanced nanovesicular systems designed to overcome traditional limitations in topical drug delivery. Methods: The review examines ultra-deformable nanovesicle technologies through comprehensive analysis of their operational mechanisms, including osmotic gradient exploitation in transfersomes and ethanol-facilitated lipid fluidization in transethosomes. Performance comparisons with conventional formulations across various therapeutic applications were conducted to assess clinical efficacy and delivery capabilities. Results: These nanovesicular systems demonstrate superior performance in delivering diverse therapeutic agents to targeted skin layers while effectively minimizing systemic absorption. The analysis reveals significant advantages over traditional formulations, with enhanced penetration capabilities that extend to macromolecular therapeutics and biologics when integrated with complementary technologies such as microneedle arrays and iontophoresis. Current research developments focus on addressing existing limitations through lyophilization techniques, hybrid polymer systems, and advanced manufacturing processes. Conclusion: Transfersomes and transethosomes represent a significant advancement in topical drug delivery technology, offering promising solutions to longstanding permeation challenges. The future trajectory toward personalized formulations and sustainable production methods using plant-derived components indicates their potential to fundamentally redefine treatment approaches in dermatology, oncology, and pain management, establishing minimally invasive yet highly effective therapeutic options as the standard in patient care.

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References

Abdellatif, A. A. H., Aldosari, B. N., Al-Subaiyel, A., Alhaddad, A., Samman, W. A., Eleraky, N. E., Elnaggar, M. G., Barakat, H., & Tawfeek, H. M. (2023). Transethosomal Gel for the Topical Delivery of Celecoxib: Formulation and Estimation of Skin Cancer Progression. Pharmaceutics, 15(1), 22. https://doi.org/10.3390/pharmaceutics15010022

Abdulbaqi, I. M., Darwis, Y., Assi, R. A., & Khan, N. A. K. (2018). Transethosomal Gels as Carriers for the Transdermal Delivery Of Colchicine: Statistical Optimization, Characterization, and Ex Vivo Evaluation. Drug Design, Development and Therapy, 12, 795–813. https://doi.org/10.2147/DDDT.S158018

Abdulbaqi, I. M., Darwis, Y., Khan, N. A. K., Assi, R. A., & Khan, A. A. (2016). Ethosomal Nanocarriers: The Impact of Constituents and Formulation Techniques on Ethosomal Properties, In Vivo Studies, and Clinical Trials. International Journal of Nanomedicine, 11, 2279–2304. https://doi.org/10.2147/IJN.S105016

Adnan, M., Afzal, O., S. A. Altamimi, A., Alamri, M. A., Haider, T., & Faheem Haider, Md. (2023). Development And Optimization of Transethosomal Gel of Apigenin for Topical Delivery: In-Vitro, Ex-Vivo and Cell Line Assessment. International Journal of Pharmaceutics, 631, 122506. https://doi.org/https://doi.org/10.1016/j.ijpharm.2022.122506

Akombaetwa, N., Ilangala, A. B., Thom, L., Memvanga, P. B., Witika, B. A., & Buya, A. B. (2023). Current Advances in Lipid Nanosystems Intended for Topical and Transdermal Drug Delivery Applications. Pharmaceutics, 15(2), 656. https://doi.org/10.3390/pharmaceutics15020656

Al-Ameri, A. A. F., & Al-Gawhari, F. J. (2024). Formulation Development of Meloxicam Binary Ethosomal Hydrogel for Topical Delivery: In Vitro and In Vivo Assessment. Pharmaceutics, 16(7), 898. https://doi.org/10.3390/pharmaceutics16070898

AL-Japairai, K., Almurisi, S. H., Abdul-Halim, N., & Mahmood, S. (2024). Dissolving Microneedle Integrated with Benidipine Loaded Ethosomes for Transdermal Delivery. Surfaces and Interfaces, 52, 104903. https://doi.org/https://doi.org/10.1016/j.surfin.2024.104903

Allam, A. A., Fathalla, D., Safwat, M. A., & Soliman, G. M. (2022). Transferosomes Versus Transethosomes for the Dermal Delivery For Minoxidil: Preparation and In Vitro/Ex Vivo Appraisal. Journal of Drug Delivery Science and Technology, 76, 103790. https://doi.org/https://doi.org/10.1016/j.jddst.2022.103790

Anwar, E., Ramadon, D., & Ardi, G. D. (2018). Novel Transethosome Containing Green Tea (Camellia sinensis L. Kuntze) Leaf Extract for Enhanced Skin Delivery of Epigallocatechin Gallate: Formulation and In Vitro Penetration Test. International Journal of Applied Pharmaceutics, 10(1), 299–302. https://doi.org/10.22159/ijap.2018.v10s1.66

Aodah, A. H., Hashmi, S., Akhtar, N., Ullah, Z., Zafar, A., Zaki, R. M., Khan, S., Ansari, M. J., Jawaid, T., Alam, A., & Ali, M. S. (2023). Formulation Development, Optimization by Box–Behnken Design, and In Vitro and Ex Vivo Characterization of Hexatriacontane-Loaded Transethosomal Gel for Antimicrobial Treatment for Skin Infections. Gels, 9(4), 322. https://doi.org/10.3390/gels9040322

Aprianti, I., Iskandarsyah, & Setiawan, H. (2023). Diflunisal Transethosomes for Transdermal Delivery: Formulation and Characterization. International Journal of Applied Pharmaceutics, 15(3), 61–66. https://doi.org/10.22159/ijap.2023v15i3.47691

Ascenso, A., Raposo, S., Batista, C., Cardoso, P., Mendes, T., Praça, F. G., Bentley, M. V. L. B., & Simões, S. (2015). Development, Characterization, and Skin Delivery Studies of Related Ultradeformable Vesicles: Transfersomes, Ethosomes, and Transethosomes. International Journal of Nanomedicine, 10, 5837–5851. https://doi.org/10.2147/IJN.S86186

Azimi, M., Khodabandeh, M., Deezagi, A., & Rahimi, F. (2019). Impact of the Transfersome Delivered Human Growth Hormone on the Dermal Fibroblast Cells. Current Pharmaceutical Biotechnology, 20(14), 1194–1202. https://doi.org/10.2174/1389201020666190809120333

Bajaj, K. J., Parab, B. S., & Shidhaye, S. S. (2021). Nano-Transethosomes: A Novel Tool for Drug Delivery Through Skin. Indian Journal of Pharmaceutical Education and Research, 55(1), s1–s10. https://doi.org/10.5530/ijper.55.1s.33

Balata, G. F., Faisal, M. M., Elghamry, H. A., & Sabry, S. A. (2020). Preparation and Characterization of Ivabradine HCl Transfersomes for Enhanced Transdermal Delivery. Journal of Drug Delivery Science and Technology, 60, 101921. https://doi.org/https://doi.org/10.1016/j.jddst.2020.101921

Basto, R., Andrade, R., Nunes, C., Lima, S. A. C., & Reis, S. (2021). Topical Delivery of Niacinamide to Skin Using Hybrid Nanogels Enhances Photoprotection Effect. Pharmaceutics, 13(11), 1968. https://doi.org/10.3390/pharmaceutics

Bendas, E. R., & Tadros, M. I. (2007). Enhanced Transdermal Delivery of Salbutamol Sulfate Via Ethosomes. AAPS PharmSciTech, 8(4), 107. https://doi.org/10.1208/pt0804107

Bhasin, B., & Londhe, V. Y. (2018). An Overview of Transfersomal Drug Delivery. International Journal of Pharmaceutical Sciences and Research, 9(6), 2175. https://doi.org/10.13040/IJPSR.0975-8232.9(6).2175-84

Bin Jardan, Y. A., Ahad, A., Raish, M., & Al-Jenoobi, F. I. (2023). Preparation and Characterization of Transethosome Formulation for the Enhanced Delivery of Sinapic Acid. Pharmaceutics, 15(10), 2391. https://doi.org/10.3390/pharmaceutics15102391

Bnyan, R., Khan, I., Ehtezazi, T., Saleem, I., Gordon, S., O’Neill, F., & Roberts, M. (2019). Formulation And Optimisation of Novel Transfersomes for Sustained Release of Local Anaesthetic. Journal of Pharmacy and Pharmacology, 71(10), 1508–1519. https://doi.org/10.1111/jphp.13149

Bos, J. D., & Meinardi, M. M. H. M. (2000). The 500 Dalton Rule for the Skin Penetration of Chemical Compounds and Drugs. Experimental Dermatology, 9(3), 165–169. https://doi.org/10.1034/j.1600-0625.2000.009003165.x

Cevc, G. (2003). Transdermal Drug Delivery of Insulin with Ultradeformable Carriers. Clinical Pharmacokinetics, 42(5), 461–474. https://doi.org/10.2165/00003088-200342050-00004

Cevc, G., & Blume, G. (1992). Lipid Vesicles Penetrate into Intact Skin Owing to the Transdermal Osmotic Gradients and Hydration Force. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1104(1), 226–232. https://doi.org/https://doi.org/10.1016/0005-2736(92)90154-E

Cevc, G., & Blume, G. (2003). Biological Activity and Characteristics of Triamcinolone-Acetonide Formulated with The Self-Regulating Drug Carriers, Transfersomes®. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1614(2), 156–164. https://doi.org/https://doi.org/10.1016/S0005-2736(03)00172-X

Cevc, G., & Blume, G. (2004). Hydrocortisone and Dexamethasone in Very Deformable Drug Carriers Have Increased Biological Potency, Prolonged Effect, and Reduced Therapeutic Dosage. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1663(1), 61–73. https://doi.org/https://doi.org/10.1016/j.bbamem.2004.01.006

Cevc, G., Blume, G., & Schätzlein, A. (1997). Transfersomes-Mediated Transepidermal Delivery Improves the Regio-Specificity and Biological Activity of Corticosteroids In Vivo. Journal of Controlled Release, 45(3), 211–226. https://doi.org/https://doi.org/10.1016/S0168-3659(96)01566-0

Cevc, G., Gebauer, D., Stieber, J., Schätzlein, A., & Blume, G. (1998). Ultraflexible Vesicles, Transfersomes, Have An Extremely Low Pore Penetration Resistance and Transport Therapeutic Amounts of Insulin Across the Intact Mammalian Skin. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1368(2), 201–215. https://doi.org/https://doi.org/10.1016/S0005-2736(97)00177-6

Chaurasiya, P., Ganju, E., Upmanyu, N., Ray, S. K., & Jain, P. (2019). Transfersomes: A Novel Technique for Transdermal Drug Delivery. Journal of Drug Delivery and Therapeutics, 9(1), 279–285. https://doi.org/10.22270/jddt.v9i1.2198

Chowdary, P., Padmakumar, A., & Rengan, A. K. (2023). Exploring the Potential of Transethosomes in Therapeutic Delivery: A Comprehensive Review. MedComm – Biomaterials and Applications, 2(4), e59. https://doi.org/https://doi.org/10.1002/mba2.59

Chowdary, P., Puppala, E. R., Putta, C. L., Maddila, J. R., Pulavarthy, V., Prasad, V. V. S. R., & Rengan, A. K. (2025). Hyaluronic-Acid-Functionalized Tofacitinib Loaded Transethosomes for Targeted Drug Delivery in Rheumatoid Arthritis. ACS Applied Bio Materials, 8(2), 1594–1606. https://doi.org/10.1021/acsabm.4c01743

Cunha, J., Latocheski, E., Fidalgo, A. C. D., Gerola, A. P., Marin, C. F. de F., & Ribeiro, A. J. (2025). Core-Shell Hybrid Liposomes: Transforming Imaging Diagnostics and Therapeutic Strategies. Colloids and Surfaces B: Biointerfaces, 251, 114597. https://doi.org/https://doi.org/10.1016/j.colsurfb.2025.114597

De Leo, V., Milano, F., Agostiano, A., & Catucci, L. (2021). Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles. Polymers, 13(7), 1027. https://doi.org/10.3390/polym13071027

Dehaghani, M. Z., Mahapatra, D., & Joseph, T. M. (2021). Transethosomes: Novel Technology for Skin Delivery of Drugs. International Journal of Medical & Pharmaceutical Sciences, 11(08), 1-5. https://doi.org/10.31782/ijmps.2021.11801

Eleraky, N. E., El-Badry, M., Omar, M. M., El-Koussi, W. M., Mohamed, N. G., Abdel-Lateef, M. A., & Hassan, A. S. (2023). Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2. International Journal of Nanomedicine, 18, 5831–5869. https://doi.org/10.2147/IJN.S423251

Estupiñán, Ó., Rendueles, C., Suárez, P., Rey, V., Murillo, D., Morís, F., Gutiérrez, G., Blanco-López, M. D. C., Matos, M., & Rodríguez, R. (2021). Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas. Journal of Clinical Medicine, 10(7), 1358. https://doi.org/10.3390/jcm10071358

Ferrara, F., Benedusi, M., Sguizzato, M., Cortesi, R., Baldisserotto, A., Buzzi, R., Valacchi, G., & Esposito, E. (2022). Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells. Pharmaceutics, 14(5), 1038. https://doi.org/10.3390/pharmaceutics14051038

Grit, M., & Crommelin, D. J. A. (1993). Chemical Stability of Liposomes: Implications for Their Physical Stability. Chemistry and Physics of Lipids, 64(1), 3–18. https://doi.org/https://doi.org/10.1016/0009-3084(93)90053-6

Gujjar, M., & Banga, A. K. (2014). Iontophoretic and Microneedle Mediated Transdermal Delivery of Glycopyrrolate. Pharmaceutics, 6(4), 663–671. https://doi.org/10.3390/pharmaceutics6040663

Published

2025-06-07

How to Cite

Widayanti Supraba, Husni, P., & Chaerunisaa, A. Y. (2025). Beyond the Skin Barrier: How Transfersomes and Transethosomes are Revolutionizing Topical Therapies. Ad-Dawaa’ Journal of Pharmaceutical Sciences, 8(1). Retrieved from https://journal.uin-alauddin.ac.id/index.php/addawaa/article/view/57146

Issue

Vol. 8 No. 1 (2025): on progress

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