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

Abstract

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