Systematic investigation of fabrication conditions of nanocarrier based on carboxymethyl chitosan for sustained release of insulin

pH-responsive nanoparticles (NPs) comprised of degradable carboxymethyl chitosan (CMCS) crosslinked with CaCl2 were simply prepared via ionic gelation. Fabrication conditions including insulin dosage, CMCS concentration, and crosslinking density were systematically investigated for insulin loading and release in vitro. The encapsulation efficiencies (EE), loading capacity (LC) and average size of the NPs decreased with the increasing insulin concentrations (<0.192 mg/mL), while they notably increased as the insulin dosage was above 0.192 mg/mL. When the concentration of CMCS increased from 0.5 to 2.0 mg/mL, the EE of the NPs reduced while the size of the NPs increased. We further demonstrated that crosslinking density offered a simple method for tuning the properties of the NPs towards various insulin concentrations. The mass ratio 10:5 of CMCS to CaCl2 exhibited the optimal performance at higher insulin concentration, whereas a higher crosslinking density of 10:7 (m:m) gave the optimal performance at low insulin concentration. The cumulative release of insulin from insulin loaded NPs decreased with the elevating crosslinking density. These findings not only provided a better understanding of the synthesis of CMCS NPs but also contributed to the practical applications of insulin loading and release.