Lipid and electroosmosis enhanced transdermal delivery of insulin by electroporation.
Transdermal transport of insulin and extraction of interstitial glucose under anodal iontophoresis (electroosmosis) following electroporation in the presence of 1,2-dimyristoylphophatidylserine (DMPS) was studied. An earlier study showed that DMPS increased the transport of insulin across porcine epidermis under electroporation by approximately fourfold. It was suggested that DMPS increased the lifetime of electropores in the epidermis resulting in an enhanced transport of permeants. When electroosmosis was applied across the epidermis following electroporation with DMPS, the enhancement of insulin transport was approximately 18-fold over electroporation alone. When the same strategy was applied to extract interstitial glucose, the enhancement was approximately 23-fold over electroporation alone. Real-time transdermal insulin transport kinetics was measured using FITC-labeled insulin and a custom-made vertical diffusion apparatus that had a fluorescence cuvette as the receiver compartment. Insulin transport by electroporation alone showed a nonlinear kinetics that is most likely due to the resealing of the electropores with time. The transport kinetics when electroporation was carried out in the presence of DMPS was more linear, confirming earlier studies that suggested the DMPS stabilizes transport paths formed by electroporation. The data suggests that in vivo, noninvasive insulin delivery to therapeutic levels and glucose extraction may be achieved by combining electroporation with anionic lipids and electroosmosis.
Murthy
S Narasimha
SN
Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Zhao
Ya-Li
YL
Marlan
Khin
K
Hui
Sek Wen
SW
Kazim
A Latif
AL
Sen
Arindam
A
D000279:Administration, Cutaneous; D000818:Animals; D001693:Biological Transport, Active; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004563:Electrochemistry; D018274:Electroporation; D005079:Excipients; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008055:Lipids; D008081:Liposomes; D009995:Osmosis; D010718:Phosphatidylserines; D013552:Swine
D004337:Drug Carriers; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008081:Liposomes; D010718:Phosphatidylserines; C042859:dimyristoylphosphatidylserine; D005947:Glucose