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.
Zhang
Q
Q
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, People's Republic of China.
Shen
Z
Z
Nagai
T
T
D000818:Animals; D001786:Blood Glucose; D004333:Drug Administration Routes; D004659:Enbucrilate / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013997:Time Factors; D014132:Trachea
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D004659:Enbucrilate