This study focuses on the development of composite hydrogel of iota-carrageenan loaded with methotrexate – mainstay therapeutic agent administered for treatment of autoimmune disorders and several types of cancer. Despite the good efficiency, methotrexate exhibits serious and sometime life-threatening adverse effects. Topical administration of methotrexate in the form of hydrogels can decrease the high toxicity of this drug. However, low aqueous solubility of methotrexate significantly limits its loading efficiency into hydrogels. In this connection, modified β-cyclodextrins, being more convenient for practical use in comparison with the native cyclodextrins, were employed to improve the aqueous solubility of methotrexate. To this end, (2-hydroxy-3-N,N,N-trimethylamino)propyl-β-cyclodextrin (NH2-βCD) displaying more pronounced solubilizing effect compared with methyl- and hydroxypropyl-β-cyclodextrins was used as solubilizer for methotrexate loaded into iota-carrageenan hydrogel. The prepared composite hydrogels were analyzed for their rheological and pharmaceutically important parameters. It was demonstrated that NH2-βCD affects the gelation process due to the binding with polar groups of iota-carrageenan. Complex formation of methotrexate with NH2-βCD has influence on the release and permeation activity of the drug. The obtained results showed that methotrexate loaded in iota-carrageenan hydrogel exhibits a sustained release.
