Evidence for lymphatic transport of insulin by topically applied biphasic vesicles.
The cutaneous delivery pathway through the lymphatics of a novel transdermal lipid-based delivery system (biphasic vesicles), which was previously shown to deliver sustained physiological levels of basal insulin in a pain-free manner across the skin, was evaluated in a diabetic rat model. Transdermal patches (one per rat) containing insulin in biphasic vesicles (1-10 mg recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 73 h. Blood glucose was monitored approximately every 2-10 h using a Lifescan glucose meter. Inguinal lymph node insulin levels were analysed by ELISA. Insulin in the lymph nodes increased in a dose- and time-dependent manner. Maximal transdermal insulin concentrations in the lymph nodes were observed with both 140 IU (5 mg: 43.0 +/- 18.0 microIU mg(-1) (mean +/- s.e.m., n = 4)) and 280 IU (10 mg: 48.0 +/- 19.6 microIU mg(-1) (mean +/- s.e.m., n = 4)) doses of recombinant insulin at t = 73 h. The level of insulin in the lymph nodes after subcutaneous injection of 1 mg insulin at the peak blood glucose response was 35.8 microIU mg(-1) (n = 2), before falling to 0.35 microIU mg(-1) by t = 48 h (n = 2). The lymphatics is involved in the transdermal insulin delivery by biphasic vesicles. This is the first report on the lymphatic transport of a protein after non-invasive topical application on the skin.
King
Martin J
MJ
PharmaDerm Laboratories Ltd., #109-111 Research Drive, Saskatoon, SK S7N 3R2, Canada.
Michel
Deborah
D
Foldvari
Marianna
M
D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000188:drug therapy; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008208:Lymphatic System / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin