In-Vitro and Ex-Vivo Evaluation of Transfersomal Gel of Methotrexate
Keywords:Methotrexate, Transfesomes, Transdermal flux, Skin permeation, Ex-vivo
Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.
Alkilani AZ, McCrudden MTC, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics 2015;7(4):470.
Arpitha M, Dhurke R. Mupirocin loaded Transfersomal Gel for Topical Delivery. Int J Recent Sci Res. 2019;10(7):33398-402.
dos Santos AM, Carvalho FC, Teixeira DA, Azevedo DL, de Barros WM, Gremião MPD. Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation. Int J Pharm. 2017;524(1-2):330-8.
Duangjit S, Opanasopit P, Rojanarata T, Ngawhirunpat T. Characterization and In Vitro skin permeation of meloxicam-loaded liposomes versus transfersomes. J Drug Deliv. 2011;2011:1-9.
Gupta R, Singhal M, Nimisha N. Transferosomes as an efficient carrier system for better therapeutic response of targeted drug delivery system. Res J Pharm Technol. 2022;26;15 (2):913-20.
Jana S, Manna S, Nayak AK, Sen KK, Basu SK. Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery. Colloids Surf B. 2014;114:36-44.
Kapoor K, Pandit V, Nagaich U. Topical methotrexate cubosomes in treatment of rheumatoid arthritis: Ex-vivo and in-vivo studies. Res J Pharm Technol . 2021;14(2):991-6.
Khan MA, Pandit J, Sultana Y, Sultana S, Ali A, Aqil M, et al. Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer treatment: in vitro characterization and in vivo study. Drug Deliv. 2015;22(6):795-802.
Lee SY, Kim CY, Nam TG. Ruthenium complexes as anticancer agents: A brief history and perspectives. Drug Des Dev Ther. 2020;14:5375-92.
Luki´c M; Panteli´c I, Savi´c SD. Towards Optimal pH of the Skin and Topical Formulations: From the Current State of the Art to Tailored Products. Cosmetics. 2021;8(3):69.
Luqmani DMR, Cox M. Getting Established on DMARD Therapy. Natl Rheum Arthitis Soc. 2016;1-8.
Malakar J, Sen SO, Nayak AK, Sen KK. Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. Saudi Pharm J. 2012;20(4):355-63.
Marwah H, Garg T, Rath G, Goyal AK. Development of transferosomal gel for trans-dermal delivery of insulin using iodine complex. Drug Deliv . 2016;23(5):1636-44.
Maurya SD, Agrawal S, Tilak VK, Dhakar RC, Singh A, Maurya G. Enhanced Transdermal Delivery of Indinavir Sulfate Via Transfersomes. Int J Compr Pharm. 2010;1(6):1-7.
Mehaneesha K, Rishab P, Seetharam SS, Mathias L, Chand S, Varghese TP, et al. A retrospective study on drug utilisation pattern in management of rheumatoid arthritis. Res J Pharm Technol . 2020;13(11):5263-6.
Merine H, Merine H. Controlled release of antipyrine from tablets using synthesized copolymers as matrices in gastric medium. Indian J Pharm Educ Res. 2015;49(4):301-8.
Modi C, Patel V, Bharadia P. Transdermal drug delivery of Methotrexate: Formulation, Optimization and characterization for developing design space. Pharma Sci Monit. 2017;8(3):190-213.
Nakanishi T, Kaiho F, Hayashi M. Improvement of drug release rate from carbopol 934P formulation. Chem Pharm Bull. 1998;46(1):171-3.
Opatha SAT, Titapiwatanakun V, Chutoprapat R. Transfersomes: A promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics. 2020;12(9):1-23.
Pandey S, Misra SK, Sharma N. Ethosomes - A novelize vesicular drug delivery system. Res J Pharm Technol . 2017;10(9):3223-32.
Patel R, Singh SK, Singh S, Sheth NR, Gendle R. Development and characterization of curcumin loaded transfersome for transdermal delivery. J Pharm Sci Res. 2009;1(4):71-80.
Rajan R, Jose S, Mukund VPB, Vasudevan DT. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation. J Adv Pharm Technol Res. 2011;2(3):138-143.
Roy N, Saha N, Saha P. Stability study of novel medicated hydrogel wound dressings. Int J Polym Mater Polym Biomater. 2013;62(3):150-6.
Samanthula KS, Satla SR, Bairi AG. Development, In-Vitro and Ex-Vivo Evaluation of Muco-adhesive Buccal patches of Candesartan cilexetil . Res J Pharm Technol . 2019;12(6):3038-44.
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. 2021;16(10):819-37.
Sandhya Lekshmi S, Antony R, Sidharthan N, Kammath G, Anila KN. Methotrexate induced lung toxicity - A case report. Res J Pharm Technol . 2017;10(10):3458-60.
Saraf S, Jeswani G, Kaur CD, Saraf S. Development of novel herbal cosmetic cream with Curcuma longa extract loaded transfersomes for antiwrinkle effect. African J Pharm Pharmacol. 2011;5(8):1054-62.
Sarwa KK, Mazumder B, Rudrapal M, Verma VK. Potential of capsaicin-loaded transfersomes in arthritic rats. Drug Deliv . 2015;22(5):638-46.
Shivanand P, Manish G, Viral D, Jarina F. Transferosomes : A novel approach for transdermal drug delivery. Der Pharm Lett. 2009;1(2):143-50.
Surini S, Nastiti PD, Putri AR, Putri KSS. Formulation of Andrographollide Transfersomes gel For transdermal delivery: A Preliminary Study. Int J Appl Pharm. 2020;12(1):187-91.
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