Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats

• Published in: Diabetes technology & therapeutics Vol. 4; no. 4; p. 479
• Main Authors: King, Martin J, Badea, Ildiko, Solomon, Jason, Kumar, Praveen, Gaspar, Kimberly J, Foldvari, Marianna
• Format: Journal Article
• Language: English
• Published: United States 2002
• Subjects: Administration, Cutaneous; Animals; Biological Availability; Delayed-Action Preparations; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Insulin - administration & dosage; Insulin - blood; Insulin - therapeutic use; Rats; Rats, Sprague-Dawley; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Skin Absorption
• ISSN: 1520-9156
• DOI: 10.1089/152091502760306562

Noninvasive transdermal insulin delivery could provide diabetic patients with sustained physiological levels of basal insulin in a pain-free manner. We have developed a novel transdermal lipid-based system (Biphasix) suitable for macromolecule delivery across the skin. The objective of this study was to evaluate the pharmacological effects of the Biphasix-insulin delivery system in a diabetic rat model. Transdermal patches (one per animal) containing Biphasix-insulin formulation (10 mg of recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 48 h. Blood glucose was monitored every 2-4 h using a Lifescan glucose meter. Serum insulin levels were analysed by enzyme-linked immunosorbent assay. A decrease in blood glucose of 43.7 +/- 3.8% (mean +/- SEM, n = 25) was observed compared with initial blood glucose levels. The duration of the response was 51.5 +/- 3.7 h (mean +/- SEM, n = 25). Serum insulin after application of the transdermal Biphasix-insulin patch was 20.08 +/- 5.44 micro IU/mL (mean +/- SEM, n = 13) during the steady state, which was not statistically different from the insulin levels obtained 2 h after subcutaneous injection of 1 mg of recombinant human insulin solution. Insulin bioavailability from the transdermal Biphasix-insulin patches was 21.5 +/- 6.9% (mean +/- SEM, n = 13) based on serum insulin and 39.5 +/- 8.5% (mean +/- SEM, n = 25) based on the pharmacodynamic blood glucose-lowering effects. The Biphasix system successfully delivered insulin transdermally, as evidenced by a significant sustained decrease in blood glucose in diabetic rats, with a corresponding increase in serum insulin. These results support the feasibility of developing a transdermal insulin patch for human applications.