Disulfide cross-linked biodegradable polyelectrolyte nanoparticles for the oral delivery of protein drugs

Polyelectrolyte nanoparticles were prepared by mixing chitosan (CS) and polyaspartic acid functionalized with cysteamine (PASP-CA) under mild conditions. The nanoparticles (NPs) included thiol moieties that were cross-linked to render the NPs stable at physiological pH. It was demonstrated that reacting the thiol moieties to form disulfide bonds led to improved stability. NPs without disulfide bonds were readily deconstructed at physiological pH. The disulfide bond cross-linked NPs can remain more stable in physiological pH solution and decrease the loss of protein drugs caused by simulating the gastric pH environment, and can release the drugs in the simulated pH environment of the intestine. This approach has potential for the in vivo application of NPs for the oral delivery of protein drugs.