Tragacanth gum-deep eutectic solvent-based eutectogels for dextromethorphan transdermal delivery and induced rheumatoid arthritis treatment in rat

Abstract

A novel eutectogel of gelling natural deep eutectic solvents was developed based on the bassorin (Ba) fraction of tragacanth gum (a biological macromolecule) for transdermal delivery of dextromethorphan (DXM) in rheumatoid arthritis. The optimal eutectic combination of 1:2 malic acid and choline chloride (ChCl) was incorporated with Ba and water. The concentration of Ba used for preparing eutectogels was 2 w/w. The results indicated that eutectic mixture of ChCl and malic acid greatly enhanced the solubility of DXM by more than 1700 times (0.19 +/- 0.04 vs 324.20 +/- 2.68 mg/mL). Increasing the water content to 60 w/w in eutectogels resulted in decreased tensile strength (2.73 vs. 0.61 kg/cm2) and a narrower linear viscoelastic region in rheometry tests. All eutectogels retained their gel-like consistency at temperatures up to 80 degrees C. In texture profile analysis, eutectogels with lower water content showed more resistance to deformation than bassorin gel due to the physical cross-linking of the gelator. Cohesion tests demonstrated remarkable capacity of eutectogels to preserve structural integrity and superior adhesiveness than hydrogel counterparts. Eutectogels with 20 water content had higher permeability of DXM through rat skin. Skin flux of DXM was significantly enhanced by eutectogel containing 20 w/w of water (332.7 mg/cm2h) compared to the Ba gel with no eutectogel (just water and Ba) (57.1 mg/cm2h). In the rats treated with eutectogels containing 20 water and 10 w/w DXM, paw swelling rate and reduction of TNF-alpha levels were not statistically different with oral methotrexate. Furthermore, the histological structure of their knee joints appeared nearly normal.