Colonic delivery of methotrexate loaded dual ionic Ca2+ and SO42- crosslinked polymeric microbeads: In vitro drug releases, HT-29 cell line and in vivo roentgenographic studies

The present study was carried out for development and characterizations of the dual-crosslinked polymeric microbead system for the targeted delivery of methotrexate (MTX) for the colorectal cancer (CRC). Microbeads were prepared based on ionotropic gelation (IG) technique by utilizing dual Ca 2+ and SO 4 2- polyions to make suitable for distal colon targeting. Those formulations were characterized for particle size, drug entrapment efficiency, swelling behaviour, SEM, FTIR, XRD, DSC and in vitro drug release profiles. The obtained particle size varied from 782.2 to 881.5 µm, with entrapment efficiencies of 72.39–89.89%, and yields of 84.28–86.44% respectively. That swelling study revealed for minimal swelling in simulated gastric fluid (pH 1.2) and maximum swelling in simulated colonic fluid (pH 7.4), respectively. In vitro release study confirmed for minimal drug release in gastric medium over 2 h and sustained release phase in colonic medium extending up to 24 h intervals. The drug release kinetics confirmed for non-Fickian type, controlled by dual mechanisms of diffusion and polymer relaxation and that were aligning closely with the Higuchi and Korsmeyer–Peppas models. Furthermore, in vitro cytotoxicity study utilizing the human colorectal adenocarcinoma HT-29 cell line and in in-vivo roentgenographic study the MTX loaded optimized microbead (MxAC) revealed for comparatively improved antiproliferative efficacy and colon targeting that confirmed for its better cellular responses and sustained drug availability throughout the study period. These findings suggested that the dual-crosslinked ALG-CHN microbeads serve as a promising approach for colon-targeted delivery of MTX in the management of CRC.