Synthesis and characterization of pre-activated thiolated chitosan nanoparticles for oral delivery of octreotide

Abstract

The study was designed to develop a nano-based delivery system for oral delivery of octreotide (OT), a peptide drug. The preactivated thiolated chitosan (PTCS) nanoparticles loaded with OT were successfully developed and characterized in vitro and in vivo. Chitosan (CS) was modified to thiolated chitosan (TCS) and preactivated thiolated chitosan (PTCS) by attaching thioglycolic acid and mercaptonicotinic acid to CS. The OT was encapsulated during NPs production, via ionic gelation technique. The PTCS-NPs had a mean size of 277 ± 19 nm, a zeta potential of +28.2 ± 3 mV with 0.2 PDI and a high payload of OT (89 ± 6%). The mucoadhesive properties of PTCS-NPs were 3- and 16-fold increased as compared to corresponding TCS and CS-NPs respectively. The sustained release of OT from PTCS-NPs over 24 h was observed with non-Fickian release kinetics. The improvement in relative oral bioavailability showed more than 4-fold improvement in elimination half-life, a ~3.4-fold enhancement in Cmax and 7.2-fold enhanced AUC(0-t) as compared to OT solution. Thus the results suggested the success of PTCS-NPs a potential oral delivery system for macromolecules due to the improved mucosal residence time, sustained release and facilitated transport via intestinal tight junctions.