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

Thieno[2,3-b]pyridine derivatives DATP have been synthesized based on Thorpe-Ziegler Cyclization. The reaction of arylidene malononitrile derivatives (I) with thiocyanoacetamide (II) in basic medium (piperidine) followed by alkylation using ethyl chloroacetate and finally, cyclization in sodium ethoxide yielded DATP. Thieno[2,3-b]pyridine-chitosan nanocomposites CS-DATP were prepared from the DATP and CS nanoparticles using sodium tripolyphosphate (TPP). CS-DATP 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 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 and CS-DATP nanocomposites exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria but CS-DATP nanocomposites showed much higher antibacterial activity compared to the DATP, which in agreement with the particle size measurements as DATP are in the bulky structure whereas, CS-DATP are in the nanostructure. The results may have applications of drug design for colon targeting.