title: Transdermal delivery of insulin by amidated pectin hydrogel matrix patch in streptozotocin-induced diabetic rats: effects on some selected metabolic parameters.
abstract: OBJECTIVE
  Studies in our laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. We therefore investigated whether the application of pectin insulin (PI)-containing dermal patches of different insulin concentrations sustain controlled release of insulin into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of diabetic symptoms in target tissues, most importantly, muscle and liver.
  
  
  METHODS
  Oral glucose test (OGT) responses to PI dermal matrix patches (2.47, 3.99, 9.57, 16.80 µg/kg) prepared by dissolving pectin/insulin in deionised water and solidified with CaCl2 were monitored in diabetic rats given a glucose load after an 18-h fast. Short-term (5 weeks) metabolic effects were assessed in animals treated thrice daily with PI patches 8 hours apart. Animals treated with drug-free pectin and insulin (175 µg/kg, s.c.) acted as untreated and treated positive controls, respectively. Blood, muscle and liver samples were collected for measurements of selected biochemical parameters.
  
  
  RESULTS
  After 5 weeks, untreated diabetic rats exhibited hyperglycaemia and depleted hepatic and muscle glycogen concentrations. Compared to untreated STZ-induced diabetic animals, OGT responses of diabetic rats transdermally applied PI patches exhibited lower blood glucose levels whilst short-term treatments restored hepatic and muscle glycogen concentrations. Plasma insulin concentrations of untreated diabetic rats were low compared with control non-diabetic rats. All PI treatments elevated plasma insulin concentrations of diabetic rats although the levels induced by high doses (9.57 and 16.80 µg/kg) were greater than those caused by low doses (2.47 and 3.99 µg/kg) but comparable to those in sc insulin treated animals.
  
  
  CONCLUSIONS
  The data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin.
  A new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported.
authors.affiliation: Schools of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Silindile I
authors.initials: SI
authors.lastname: Hadebe
authors.affiliation: Schools of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Phikelelani S
authors.initials: PS
authors.lastname: Ngubane
authors.affiliation: Schools of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Metse R
authors.initials: MR
authors.lastname: Serumula
authors.affiliation: Schools of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Cephas T
authors.initials: CT
authors.lastname: Musabayane
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D010368:Pectins / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D057968:Transdermal Patch
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010368:Pectins; D006003:Glycogen