Syringeable hydrogel based β-cyclodextrin and mixed micelles for methotrexate delivery

Herein, mixed micelles laden hydrogel with syringeable feature were designed for intra-articular route of Methotrexate (MTX). The ternary system (FP–B58) based on mixed Pluronic F127/P123 system and Brij 58 was selected to fabricate the polymeric micelle. The solubility of MTX was remarkable improved in ternary micelles system than that of the binary micells system. The MTX in FP-B58 was 16.53 ± 0.87 mg/ml, while MTX in the mixed Pluronic micelles was 12.67 ± 1.27 mg/ml. The mixed micelles laden hydrogel were obtained by host-guest interaction with β-cyclodextrin (βCD). With the addition of 6 wt% βCD into FP-B58@MTX, the sol–gel transition behaviour following a temperature change was observed, confirming the syringeable feature. Due to the enhancement in the physical network by the supplement of βCD, the kinetic release of MTX transformed from non-Fickian (micelles system) to Fickian (hydrogel system). Following the effective controlled release, the cytotoxic of MTX in hydrogel was reduced, whereas the anti-inflammatory effects was similar to raw MTX at similar dose. In conclusion, MTX-loaded mixed micelles laden hydrogel are an attractive drug delivery strategy for effectively managing and treating rheumatoid arthritis.