Enhanced pH-responsive carrier system based on alginate and chemically modified carboxymethyl chitosan for oral delivery of protein drugs: Preparation and in-vitro assessment

In this investigation a new series of biodegradable pH-responsive hydrogel microspheres were prepared, characterized and in-vitro evaluated as potential carriers for oral delivery of protein drugs. The microspheres are based on ionotropically-crosslinked mixture of sodium alginate and chemically modified carboxymethyl chitosan and coated through polyelectrolyte complexation with chitosan grafted with poly(ethylene glycol). The main objective of the developed microspheres is to survive the harsh acidity of stomach and preferably release peptide and protein drugs in intestine. Both ionotropic gelation and coating process were carried out under mild aqueous conditions, which should be appropriate for retention of biological activity of protein drugs. Swelling studies were carried out for the microspheres at 37 °C in simulated gastric and intestinal fluids. Morphology, size and in-vitro biodegradation of the microspheres were also investigated. A model protein drug was entrapped and the in-vitro drug release profiles were established. The preliminary investigation of the microspheres developed in this study showed a consistent swelling pattern, high entrapment efficiency and promising sustained release profiles of the model protein drug.