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 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.

Keywords: Antibacterial; Chitosan; Colon targeting; Drug release; Nanocomposites; Thienopyridines.