Transdermal Delivery of Insulin by Amidated Pectin Hydrogel Matrix Patch in Streptozotocin-Induced Diabetic Rats: Effects on Some Selected Metabolic Parameters

Abstract

PurposeStudies 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.MethodsOral 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, sc) acted as untreated and treated positive controls, respectively. Blood, muscle and liver samples were collected for measurements of selected biochemical parameters.ResultsAfter 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.ConclusionsThe data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin.Novelty of the WorkA new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported.

The effects of transdermal insulin treatment of streptozotocin-induced diabetic rats on kidney function and renal expression of glucose transporters

“…We have reported in another study that insulin-containing dermal patch formulation sustains slow controlled release of insulin into the bloodstream of diabetic rats with a concomitant reduction in plasma glucose concentrations. 9,37 As assessed by western blotting, PI treatment significantly decreased the renal expression of SGLT1 and GLUT1 to perhaps to reduce glucose re-absorption. These transporters which were unregulated in untreated STZ-induced diabetic rats increased the reabsorption of glucose and thus contributed to the pre-existing hyperglycemia.…”

Photothermally triggered on-demand insulin release from reduced graphene oxide modified hydrogels

“…While electrically erodible polymer gels have been proposed by Kwon et al [23], prolonged insulin delivery in diabetic rabbits was achieved using poly(lactide-ethylene-glycol) nanoparticles [24]. Insulin amidated pectin hydrogels were recently proposed as insulin delivery platforms by Hadebe et al [25]. We have recently exploited the good electrical properties of rGO thin films for efficient electrochemical release of human insulin from rGO-modified electrodes [7].…”

The Ameliorative Effect of Pectin-Insulin Patch On Renal Injury in Streptozotocin-Induced Diabetic Rats

“…Pectin-insulin dermal patches of different insulin concentrations were prepared using a previously described protocol [13]. Briefly, amidated low methoxyl pectin (6 g) was dissolved in distilled water (100 mL) and mixed by agitation for 30 minutes.…”

“…In our laboratory, we have successfully developed a transdermal pectin-insulin patch formulation that can deliver physiologically relevant insulin concentration which can maintain normal glycaemic control and ameliorate certain diabetes associated complications in streptozotocin (STZ) induced-diabetic rats [13, 14]. Accordingly, in the study, we sought to evaluate the effects of transdermal pectin-insulin patch application on markers of kidney function such as blood pressure, creatinine clearance, albumin excretion rate, kidney nephrin expression and urinary nephrin concentration.…”