Transdermal delivery of insulin by amidated pectin hydrogel matrix patch in streptozotocin-induced diabetic rats: effects on some selected metabolic parameters
Authors: Silindile I Hadebe
Cephas T Musabayane
Metse R Serumula
Phikelelani S Ngubane
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: insulin delivery routes; pectin hydrogel matrix gel; dermal patches; insulin concentrations; controlled release
Affiliations: Schools of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Abstract:  Purpose: 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. Novelty of the work: A new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported. 

Retracted: Yes

PubPeer comments:
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 2021 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0247150 Following the publication of this article [1], concerns were raised regarding results presented in Figs 1 and 6. Specifically, Fig. 1B partially overlaps with Fig. 1D. In Fig. 6, the following bands appear similar: u25cb. Left u03b2-actin panel: lanes 1 and 8, and lane 5 when flipped. u25cb. Left u03b2-actin panel: lanes 2 and 6 when flipped. u25cb. Left u03b2-actin panel: lanes 3 and 4, and lane 7 when flipped. u25cb. Right u03b2-actin panel: lanes 1 and 3. In the Fig. 6 GS panel, left u03b2-actin panel and right u03b2-actin panel irregularities have been detected between the background signal directly surrounding the bands in all lanes and the overall background signal of the blot. The original data for the figures of concern are no longer available. In light of the concerns affecting multiple figure panels that question the integrity of these data, the PLOS ONE Editors retract this article. SIH, PSN, and MRS either did not respond directly or could not be reached. CTM is deceased. Reference 1.Hadebe SI, Ngubane PS, Serumula MR, Musabayane CT (2014) Transdermal Delivery of Insulin by Amidated Pectin Hydrogel Matrix Patch in Streptozotocin-Induced Diabetic Rats: Effects on Some Selected Metabolic Parameters. PLoS ONE 9(7): e101461. https: doi.org 10.1371 journal.pone.0101461 pmid:24987850 ,