Fluorophenylboronic acid substituted chitosan for insulin loading and release

Phenylboronic acid (PBA) can form dynamical reversible chemical bonds with sugars, and has potential in glucose response and controlling insulin delivery. In this paper, 4-fluorophenylboronic acid (FPBA) was employed which could work better than normal PBA in physiological environment. Herein, FPBA-substituted chitosans (CS-FPBA) with three different molecular weights were prepared, and affecting factors on preparation, including solvent, pH, raw materials ratio, activation time and reaction time, were discussed. The glucose responsiveness and controlling insulin release properties of CS-FPBA were also determined. Results showed that the substitution of FPBA onto CS could decrease the zeta potential of CS to negative values, which was favorable for CS-FPBA to react with hydroxyl groups in biological environments. They could effectively load with insulin with approximately 50% (wt%) encapsulation efficiency in 0.5 mg/mL insulin. Also, CS-FPBA particles had significant binding efficiency to glucose, which was dramatically higher by over 6 folds compared to chitosan. The maximum releasing amount of insulin was >90% in 9 h in 3 mg/mL of glucose solution when the molecular weight of CS was 50 kDa. In summary, CS-FPBA has potential to control the release of insulin, and can regulate the release rate by controlling the molecular weight of CS.