International Journal of Drug Delivery Technology
Volume 15, Issue 3

Topical Methotrexate Loaded Nanogel for Rheumatoid Arthritis: Optimization using Box-Behnken Design and Evaluation of Anti-Arthritic Activity

Sonali B Deokate*, Smita S Pimple, P D Chaudhari, Nayan P Ajankar

Department of Pharmaceutics, Modern College of Pharmacy, Nigdi, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India 

Received: 3rd May, 2025; Revised: 12th Jun, 2025; Accepted: 29th Jun, 2025; Available Online: 25th Sep, 2025 

ABSTRACT

The present study emphases on formulation, optimization, and assessment of a methotrexate-loaded nanogel (MXT-NGs) for current topical treatment of rheumatoid arthritis. MTX, a potent antimetabolite, faces encounters as systemic toxicity, poor solubility, and non-specific distribution when administered conventionally. To overcome these limitations, nanogel formulations were developed using Carbopol 934, HPMC K15, and Tween 80, and optimized through a Box-Behnken Design (BBD) approach. Seventeen formulations (MXT-NGs-F1–MXT-NGs-F17) were evaluated for physicochemical properties including pH, viscosity, spreadability, entrapment efficiency, zeta potential, drug content, and particle size. DSC, FTIR, SEM, and XRD analyses inveterate compatibility, amorphization of drug, and nanoscale morphology. The optimized formulation (MXT-NGs-F16) exhibited favorable characteristics: entrapment efficiency (76.65%), high drug content (96.45%), small particle size (123.74 nm), and sustained drug release up to 12 hours. Ex vivo permeation also in vivo studies in a CFA-induced arthritis rat model demonstrated significantly reduced paw edema, arthritis index score, and biochemical markers of inflammation (ALT, AST, ALP, TNF-α, IL-1β) with enhanced antioxidant levels (GSH, SOD, CAT). These conclusions highlight probable of optimized methotrexate nanogel as a promising transdermal delivery system for enhanced management of rheumatoid arthritis with reduced systemic side effects.

Keywords: Methotrexate, Nanogel, Box-Behnken Design, Rheumatoid Arthritis, Topical Delivery, Sustained Release, Antioxidant Activity, Drug Permeation, Anti-inflammatory, CFA-induced Arthritis Model.

How to cite this article: Sonali B Deokate, Smita S Pimple, P D Chaudhari, Nayan P Ajankar. Topical Methotrexate Loaded Nanogel for Rheumatoid Arthritis: Optimization using Box-Behnken Design and Evaluation of Anti-Arthritic Activity. International Journal of Drug Delivery Technology. 2025;15(3):1293-1303. doi: 10.25258/ijddt.15.3.50

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