Can metabolic impairments in experimental diabetes be cured with poly(amido)amine (PAMAM) G4 dendrimers? - In the search for minimizing of the adverse effects of PAMAM administration

Poly(amido)amine (PAMAM) G4 dendrimers, given intraperitoneally to diabetic rats, have been reported to scavenge excessive blood glucose and minimize the effects of hyperglycaemia, however, at the cost of reduced survival. This paper is the first to compare the effectiveness of three different routes of PAMAM G4 administration with regard to minimizing the adverse effects of hyperglycaemia in rats. Hence, the aim of the study is to identify the most effective and the least harmful method of dendrimer administration. Control and streptozotocin-diabetic Sprague-Dawley rats were exposed to PAMAM G4 (0.5 mu mol/kg b.w.) for 60 days, administered intraperitoneally, intragastrically or subcutaneously. Intraperitoneal and subcutaneous administration of PAMAM G4 was found to be most effective in suppressing the long-term markers of hyperglycaemia, while the intragastric route appeared the least effective. Otherwise, the greatest incidence of adverse effects was associated with intraperitoneal and the lowest with subcutaneous delivery. Harmful effects of intragastrical administration were much lower compared to intraperitoneal route, but at the cost of reduced hypoglycaemizing potential. Otherwise, subcutaneous injection represents the best compromise of moderate PAMAM dendrimer toxicity and effective reduction in the markers of long-term severe hyperglycaemia in chronic experimental diabetes. (C) 2014 Elsevier B.V. All rights reserved.