Methotrexate Aspasomes Against Rheumatoid Arthritis: Optimized Hydrogel Loaded Liposomal Formulation with In Vivo Evaluation in Wistar Rats

Abstract

Aspasomes of methotrexate with antioxidant, ascorbyl palmitate, were developed and optimized using factorial design by varying parameters such as lipid molar ratio, drug to lipid molar ratio, and type of hydration buffer for transdermal delivery for disease modifying activity in rheumatoid arthritis (RA). Aspasomes were characterized by drug-excipients interaction, particle size analysis, determination of zeta potential, entrapment efficiency, and surface properties. The best formulation was loaded into hydrogel for evaluation of in vitro drug release and tested in vivo against adjuvant induced arthritis model in wistar rats, by assessing various physiological, biochemical, hematological, and histopathological parameters. Optimized aspasome formulation exhibited smooth surface with particle size 386.8 nm, high drug loading (19.41%), negative surface potential, and controlled drug release in vitro over 24 h with a steady permeation rate. Transdermal application of methotrexate-loaded aspasome hydrogel for 12 days reduced rat paw diameter (21.25%), SGOT (40.43%), SGPT (54.75%), TNFα (33.99%), IL β (34.79%), cartilage damage (84.41%), inflammation (82.37%), panus formation (84.38%), and bone resorption (80.52%) as compared to arthritic control rats. Free methotrexate-treated group showed intermediate effects. However, drug-free aspasome treatment did not show any effect. The experimental results indicate a positive outcome in development of drug-loaded therapeutically active carrier system which presents a non-invasive controlled release transdermal formulation with good drug loading, drug permeation rate, and having better disease modifications against RA than the free drug, thereby providing a more attractive therapeutic strategy for rheumatoid disease management.

Formulation Strategies for Folate-Targeted Liposomes and Their Biomedical Applications

“…A number of therapeutics, including paclitaxel (PTX) [105,106], doxorubicin (DOX) [107,108], methotrexate [109,110], cis-platin [111,112], curcumin [113,114], 5-fluorouracil [115,116], irinotecan [117,118], and nucleic acids [119,120], have been delivered via polymeric carriers [121] to cells. However, liposomes provide unique properties, as their charge, size, and surface properties can easily be tuned by selecting different ingredients of lipid mixture prior to the preparation of the liposomes.…”

Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

“…The transdermal delivery efficacy of this system was assessed in vivo using an AIA rat model. [83] Application of the hydrogel for 12 days not only reduced the rat paw diameter, histopathological scores, and proinflammatory cytokine (TNF and IL-) levels but also decreased the side effects. Further studies are needed to establish the correlation and an optimized dosage regimen for the combination of MTX and ascorbyl palmitate.…”

Hydrogels in the treatment of rheumatoid arthritis: drug delivery systems and artificial matrices for dynamic in vitro models

“…Furthermore, the group treated with free MTX exhibited intermediate effects however, the group treated with free aspasome did not show to have an effect. The results demonstrated that drug-loaded therapeutically active carrier system presented a non-invasive controlled release transdermal formulation with good drug encapsulation, drug permeation rate, and showed a more effective therapeutic effect in treatment of RA than the drug alone [52].…”

“…The lipogels delivered a significant amount of drug through the skin than the hydrogel after 24 h. The constitution of lecithin showed to affect the skin permeability increasing the capability of the lipogel. Another study developed MTX aspasomes encapsulated into a hydrogel and tested in AIA model in Wistar rats [52]. Transdermal application of MTX-loaded aspasome hydrogel in model disease demonstrated a more significant decrease of rat paw diameter, tumor necrosis factor-alpha (TNF-α), interleukin (IL-1) β, cartilage damage, inflammation, pannus formation, and bone resorption when compared to arthritic control rats after 21 days.…”