Transdermal Delivery of CaCO 3 -Nanoparticles Containing Insulin

Abstract

Background:

This study evaluates the pharmacokinetic and pharmacodynamic effects of a transdermally delivered insulin using novel CaCO₃-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 µIU/mL at 4 h with 200 µg of transdermal nanoinsulin in ddY mice, whereas that after subcutaneous injection of 3 µg of monomer insulin was 462 ± 20.9 µIU/mL at 20 min. Transdermal nanoinsulin decreased glucose levels in a dosedependent 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 µg 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 3µg 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 CaCO₃-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.