Curcumin-Loaded Transethosomal Gel for Enhanced Dermal Delivery in Arthritis

References

[1] Toumi H, Almhdie-Imjabbar A, Ibrahim N, Lespessailles E. Curcumin in arthritis: molecular mechanisms, preclinical evidence, and clinical applications. Int J Mol Sci. 2026;27(11):4894.

[2] GBD 2021 Rheumatoid Arthritis Collaborators. Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023.

[3] Cui X, Wang R, Bian P, Wu Q, Seshadri VDD, Liu L. Evaluation of antiarthritic activity of nimbolide against freund's adjuvant induced arthritis in rats. Artif Cells Nanomed Biotechnol. 2019;47(1):3391–8.

[4] Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–18.

[5] A comprehensive review of nanotechnology based drug delivery systems for osteoarthritis treatment. Nanotechnol Rev. 2025.

[6] Overcoming the skin permeation barrier: challenges and opportunities. Ther Deliv. 2015.

[7] 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):403–18.

[8] Jain S, Tiwary AK, Sapra B, Jain NK. Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS PharmSciTech. 2007;8(4):Article 111.

[9] Abdulbaqi IM, Darwis Y, Khan NA, 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;11:2279–304.

[10] Raza K, Singh B, Mahajan A, Negi P, Bhatia A, Katare OP. Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin. J Drug Target. 2011;19(4):293–302.

[11] 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;10:5837–51.

[12] Garg V, Singh H, Bimbrawh S, Singh SK, Gulati M, Vaidya Y, et al. Ethosomes and transfersomes: principles, perspectives and practices. Curr Drug Deliv. 2017;14(5):613–33.

[13] Munir M. A comprehensive review on transethosomes as a novel vesicular approach for drug delivery through transdermal route. J Liposome Res. 2024;34(1):203–18.

[14] Garg V, Singh H, Bhatia A, Raza K, Singh SK, Singh B, et al. Systematic development of transethosomal gel system of piroxicam: formulation optimization, in vitro evaluation, and ex vivo assessment. AAPS PharmSciTech. 2017;18(1):58–71.

[15] Kaur P, Garg V, Bawa P, Sharma R, Singh SK, Kumar B, et al. Formulation, systematic optimization, in vitro, ex vivo, and stability assessment of transethosome based gel of curcumin. Asian J Pharm Clin Res. 2018;11(2):41–7.

[16] Sana E, Zeeshan M, Ain QU, Khan AU, Hussain I, Khan S, et al. Topical delivery of curcumin-loaded transfersomes gel ameliorated rheumatoid arthritis by inhibiting NF-κβ pathway. Nanomedicine (Lond). 2021;16(10):819–37.

[17] Gharat S, Momin M, Panchal U, Omri A. Novel ethosomal gel formulation for enhanced transdermal delivery of curcumin and cyclosporine: a preclinical approach to rheumatoid arthritis management. Drug Deliv. 2025;32(1):2512620.

[18] Wang W, Tham PH, Ding C, Huang P, Li T, Luo J, et al. Transethosome-based topical administration systems with enhanced penetration and dual actions for treating EGFR-overexpressed cutaneous squamous cell carcinoma. Adv Funct Mater. 2024;34(24):2312838.

[19] Adin SN, Gupta I, Rashid MA, Alhahoom Y, Aqil M, Mujeeb M. Nanotransethosomes for enhanced transdermal delivery of mangiferin against rheumatoid arthritis: formulation, characterization, in vivo pharmacokinetic and pharmacodynamic evaluation. Drug Deliv. 2023;30(1):2173338.

[20] Hemida D, Shehata N, Elgiddawy N, Alfassam HE, Mahgoub SM, Mahmoud R. A QbD-optimized magnetic MOF-chitosan nanocarrier for targeted curcumin delivery and synergistic antimicrobial activity. RSC Adv. 2026;16(27):25144–73.

[21] Yasmeen, Khan MA, Iqbal Z, Aqil M. Carbopol 934-based transethosomal gel of glycyrrhizic acid for the management of skin cancer. J Drug Deliv Sci Technol. 2024;97:105825.

[22] Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B Biointerfaces. 2014;113:330–7.

[23] Yu LX, Woodcock J. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771–3.

[24] Abdulbaqi IM, Darwis Y, Assi RA, Khan NA. Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation. Drug Des Devel Ther. 2018;12:795–813.

[25] Pathan IB, Nandure H, Syed SM, Bairag S. Transdermal delivery of ethosomes as a novel vesicular carrier for paroxetine hydrochloride: in vitro evaluation and in vivo study. Marmara Pharm J. 2016;20:1–6.

[26] Ruckmani K, Sankar V. Formulation and optimization of zidovudine niosomes. AAPS PharmSciTech. 2010;11(3):1119–27.

[27] George A, Limbachiya V, Shrivastav PS. Current status and role of carbopols in oral, nasal, transdermal, topical and ophthalmic drug delivery systems. Next Mater. 2025;9.

@article{1723902,
      author = {Anand Yadav, Anoop Kumar Singh},
      title = {Curcumin-Loaded Transethosomal Gel for Enhanced Dermal Delivery in Arthritis},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {4},
      pages = {1428-1441},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1723902.pdf},
      abstract = {Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic, progressive joint disorders whose initiation and progression are driven substantially by nuclear factor-kappa B (NF-κB)-mediated transcription of pro-inflammatory cytokines, cyclooxygenase-2 and matrix metalloproteinases [1,2]. Curcumin, the principal curcuminoid of Curcuma longa, is a well-characterised inhibitor of this cascade with documented antioxidant and chondroprotective activity [1], but its clinical utility is severely constrained by extremely poor aqueous solubility, chemical instability and negligible oral bioavailability as a Biopharmaceutics Classification System (BCS) Class IV molecule [3,4]. Dermal/topical delivery directly to the peri-articular tissue offers an attractive alternative that bypasses hepatic first-pass metabolism, but the stratum corneum's densely packed lipid architecture is a formidable barrier to permeation of lipophilic phytoconstituents [6]. This review traces the evolution of vesicular nanocarrier platforms developed to overcome this barrier — liposomes, ethosomes, transfersomes and, most recently, transethosomes — and examines the rationale for transethosomes as a rationally engineered hybrid system that combines the ethanol-mediated bilayer fluidisation of ethosomes with the edge-activator-imparted elasticity of transfersomes [7,9,11,12,13,14]. We summarise the published literature on curcumin- and related phytoconstituent-loaded vesicular gels evaluated in experimental arthritis models, the Quality by Design (QbD)/Box–Behnken framework increasingly used to systematically optimise such formulations [20,23,24], and the standard physicochemical and in vitro biological evaluation parameters applied to transethosomal gels. We conclude that curcumin-loaded transethosomal gels represent a mechanistically well-supported, still-maturing formulation strategy for localised anti-arthritic therapy, with QbD-driven optimisation and rigorous in vitro evaluation frameworks positioned as the critical next steps toward eventual ex vivo and in vivo translational development.},
      keywords = {curcumin; transethosomes; ethosomes; transfersomes; liposomes; quality by design; Box–Behnken design; rheumatoid arthritis; osteoarthritis; dermal drug delivery; NF-κB},
      month = {October},
  }