RESUMO
BACKGROUND: This study evaluates the pharmacokinetic and pharmacodynamic effects of a transdermally delivered insulin using novel CaCO(3)-nanoparticles in normal mice and those with diabetes. METHODS: CaCO3-nanoparticles encapsulating insulin (nanoinsulin) were transdermally applied to the back skin of normal ddY mice and dB/dB and kkAy mice with diabetes after fasting for 1 h. Serum insulin levels of ddY mice were analyzed by enzyme immunoassay, and blood glucose of normal mice and those with diabetes was monitored. RESULTS: Maximum serum insulin was 67.1 +/- 25.9 microIU/mL at 4 h with 200 microg of transdermal nanoinsulin in ddY mice, whereas that after subcutaneous injection of 3 microg of monomer insulin was 462 +/- 20.9 microIU/mL at 20 min. Transdermal nanoinsulin decreased glucose levels in a dose-dependent manner. A maximum decrease in blood glucose of 48.3 +/- 3.9% (ddY), 32.5 +/- 9.8% (dB/dB), and 26.2 +/- 7.6% (kkAy) after 6 h was observed with 200 microg of transdermal nanoinsulin, compared with 64.1+/-1.0% (ddY), 57.9 +/-3.4% (dB/dB), and 24.1 +/- 6.7% (kkAy) after 1 h with 3 microg of subcutaneous monomer insulin. Insulin bioavailability until 6 h with transdermal nanoinsulin in ddY mice was 0.9% based on serum insulin level and 2.0% on pharmacodynamic blood glucose-lowering effects. CONCLUSIONS: This CaCO(3)-nanoparticle system successfully delivered insulin transdermally, as evidenced by a significant sustained decrease in blood glucose in normal mice and those with diabetes. These results support the feasibility of developing transdermal nanoinsulin for human applications.