Studies in our laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. We have succeeded in sustaining plasma insulin concentrations in streptozotocin (STZ)-induced diabetic rats using amidated pectin-insulin (PI) dermal patches. The non-invasive dermal patches may offer minimally invasive drug delivery in clinical applications to perhaps improve drug bioavailability and patient compliance. On the other hand, medical plants believed to be safe and cost effective than synthetic hypoglycaemic agents play important roles in the management of diabetes mellitus in developing countries where resources are meagre. We have isolated triterpenes from Syzygium aromaticum as the bioactive compounds that possess hypoglycaemic effects in experimental diabetes. However, the poor water solubility of triterpenes observed in oral administration has necessitated the evaluation of alternative methods of administration for effective diabetes management.

Accordingly, the aim of this study was to investigate whether transdermal application of Syzygium aromaticum-derived oleanolic acid patch (P-OA) formulations sustain controlled release of oleanolic acid (OA) into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of some of the complications associated with diabetes.

Topically applied P-OA patches containing various OA doses (21, 42 and 84 mg/kg) prepared by dissolving pectin/OA in deionised water with subsequent solidification with CaCl2 were evaluated for oral glucose tolerance responses in groups of STZ-induced diabetic rats. Short-term (5 weeks) effects were assessed in diabetic animals treated thrice daily with P-OA patches 8 hours apart. Animals treated with drug-free pectin and subcutaneous insulin (175 μg/kg, s.c.) acted as untreated and treated positive controls, respectively. Blood and tissue samples were collected for the measurement of selected metabolic parameters.

Blood glucose concentrations were significantly reduced following transdermal P-OA treatment thus indicating that OA was transported across the skin. The treatment also restored the reduced glycogen concentrations in muscle and hepatic tissues of diabetic animals to near normalcy. These effects were comparable to those observed in animals administered with the standard drug, s.c. insulin. However, there was no change in plasma insulin concentrations of STZ-induced diabetic rats following acute and short-term daily treatment with P-OA patches.

The data indicate successful sustained controlled release of OA into the bloodstream of STZ-induced diabetic rats via P-OA hydrogel matrix patches with a concomitant reduction in plasma glucose concentrations and amelioration of some selected metabolic parameters. POA-containing dermal patch formulations will be easy to use and will not require elaborative devices to prevent drug leakage as in solution formulations. The findings are of considerable importance because application of OA-containing dermal patches would free diabetic patients from daily bolus injections required to maintain physiologically relevant amounts of pharmacologically active insulin. The POA-containing dermal hydrogel matrix patch would also provide patients with pain-free self-administration of anti-diabetic drugs thereby improving compliance.

Transdermal delivery of Syzygium aromaticum-derived oleanolic acid by dermal patches in STZ-induced diabetic rats.