Design, synthesis, characterization and biological evaluation of Thieno[2,3?b]pyridines?chitosan nanocomposites as drug delivery systems for colon targeting

Article abstract of DOI:10.1016/j.carres.2020.107990

Thieno[2,3?b]pyridine derivatives DATP_a?c have been synthesized based on Thorpe?Ziegler Cyclization. The reaction of arylidene malononitrile derivatives (I_a?c) with thiocyanoacetamide (II) in basic medium (piperidine) followed by alkylation using ethyl chloroacetate and finally, cyclization in sodium ethoxide yielded DATP_a?c. Thieno[2,3?b]pyridine?chitosan nanocomposites CS?DATP_a?c were prepared from the DATP_a?c and CS nanoparticles using sodium tripolyphosphate (TPP). CS?DATP_a?c nanocomposites were characterized using FTIR, TEM and XRD techniques and showed a relatively narrow size distribution of monodispersed nanoparticles with the average size of 14–78 nm. The in vitro release studies of CS?DAΤP_a?c nanocomposites were investigated and showed that the drug release rate is pH-dependent and the trend is as follows: basic > neutral > acidic. The faster release rate in basic medium effectively prolongs drug delivery in gastric pH. Additionally, the antibacterial investigation showed that DATP_a?c and CS?DATP_a?c nanocomposites exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria but CS?DATP_a?c nanocomposites showed much higher antibacterial activity compared to the DATP_a?c, which in agreement with the particle size measurements as DATP_a?c are in the bulky structure whereas, CS?DATP_a?c are in the nanostructure. The results may have applications of drug design for colon targeting.