Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats.

Insulin-loaded polybutylcyanoacrylate nanoparticles were prepared by emulsion polymerization. The mean diameter of the nanoparticles was 254.7 nm with a polydispersity of 0.064. The associating ratio of insulin to the nanoparticles reached 79.1%. Studies on in vitro release kinetics showed that release profiles can be modeled using a biexponential function and the burst effect was obvious. After various doses of insulin-loaded nanoparticles were intratracheally given to normal rats, significant decrease of glucose level was achieved at each dose group from 5 to 20 IU kg-1. The minimum blood glucose concentration reached 46.9%, 30.4% and 13.6% of the initial level after pulmonary delivery of 5, 10 and 20 IU kg-1 insulin-loaded nanoparticles to normal rats, respectively. The time to reach the minimum blood glucose level (Tmin) was 4, 4 and 8 h for three doses, respectively. The duration of glucose level below 80% of insulin-loaded nanoparticles was much longer than that of insulin solution at every dose. Relative pharmacological bioavailability of insulin-loaded nanoparticles by pulmonary administration was 57.2% over the same formulation by subcutaneous administration.