Improving the hypoglycemic effect of insulin via the nasal administration of deep eutectic solvents

This study aimed to develop biocompatible deep eutectic solvents (DESs) as carriers for improving the nasal delivery of insulin. The DES was prepared from malic acid and choline chloride broadly used in foods, drugs, or cosmetics as biocompatible additives. The DES of choline chloride and malic acid (CM-DES) demonstrated lower melting point (-59.1 °C) and higher viscosity (120,000 cP) compared with hydrogels based on sodium carboxyl methyl cellulose (CMC-Na). The conformational structure of insulin does not change in CM-DES as characterized by circular dichroism. The in vitro results showed that CM-DES dissociated gradually but did not disintegrate immediately upon contact with water. CM-DES was able to improve the hypoglycemic effect of insulin significantly at different doses compared with hydrogels or solutions of insulin, which could be ascribed to facilitated penetration of insulin across the nasal epithelia by CM-DES. The hypoglycemic effect of CM-DES loading insulin at a dose of 25 IU/kg was similar to that of subcutaneous insulin at 1 IU/kg. In addition, no evident toxicity to nasal epithelia was observed after nasal administration to rats for seven consecutive days. In conclusion, CM-DES showed promising potential in enhancing the hypoglycemic effect of insulin via the nasal route.