title: Electroporation of polymeric nanoparticles: an alternative technique for transdermal delivery of insulin.
abstract: OBJECTIVE
  The aim was to study transdermal electroporation of insulin-loaded nanocarriers as a methodology for delivering macromolecules.
  
  
  METHODS
  The efficacy of electroporation of insulin as solution and nanoparticles was compared in vitro and in vivo. Histology and confocal laser scanning microscopy were used to assess the effects of electroporation on skin structure, whereas the latter also demonstrated the depth of permeation of the nanoparticles. In vivo studies were performed on streptozotocin-diabetic male Wistar rats and compared with subcutaneous administration.
  
  
  RESULTS
  A linear increase in insulin flux was noted on increasing the applied voltage (R(2) = 0.9514), the number of pulses (R(2) = 0.8515), and the pulse length (R(2) = 0.9937). Electroporation of nanoparticles resulted in fourfold enhancement in insulin deposition in rat skin in contrast to solution. In vivo studies showed maximum reduction of 77 ± 5% (87.2 ± 6.4 mIU/mL, t = 2 hours) and 85 ± 8% (37.8 ± 10.2 mIU/mL, t = 4 hours) in blood glucose levels for solution and nanoparticles, respectively, with therapeutic levels maintained for 24 and 36 hours.
  
  
  CONCLUSIONS
  Overall, electroporation of polymeric nanosystems proved to be an ideal alternative to injectable administration.
authors.affiliation: Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, India.
authors.forename: Rachna
authors.initials: R
authors.lastname: Rastogi
authors.forename: Sneh
authors.initials: S
authors.lastname: Anand
authors.forename: Veena
authors.initials: V
authors.lastname: Koul
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry; D018274:Electroporation / Q000379:methods; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D013311:Streptozocin