Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats.
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.
King
Martin J
MJ
PharmaDerm Laboratories Ltd, Saskatoon, Saskatchewan, Canada.
Badea
Ildiko
I
Solomon
Jason
J
Kumar
Praveen
P
Gaspar
Kimberly J
KJ
Foldvari
Marianna
M
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012869:Skin Absorption
D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007328:Insulin; D011994:Recombinant Proteins