2 January 2024 | Nicholas J. Hunt, Glen P. Lockwood, Scott J. Heffernan, Jarryd Daymond, Meng Ngu, Ramesh K. Narayanan, Lara J. Westwood, Biswaranjan Mohanty, Lars Esser, Charlotte C. Williams, Zdenka Kuncic, Peter A. G. McCourt, David G. Le Couteur, Victoria C. Cogger
This study presents an oral nanotherapeutic formulation of insulin conjugated to silver sulfide quantum dots (Ag2SQDs) coated with a chitosan/glucose copolymer (CS/GS). The formulation is pH responsive, insoluble in acidic environments, and shows increased absorption in human duodenum explants and *Caenorhabditis elegans* at neutral pH. It is sensitive to glucosidase enzymes, which trigger insulin release. The formulation distributes to the liver in mice and rats after oral administration, promoting a dose-dependent reduction in blood glucose without causing hypoglycemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose without adverse effects. The study demonstrates the potential of this formulation to control blood glucose levels orally without hypoglycemic episodes, addressing the escalating burden of diabetes and its complications.This study presents an oral nanotherapeutic formulation of insulin conjugated to silver sulfide quantum dots (Ag2SQDs) coated with a chitosan/glucose copolymer (CS/GS). The formulation is pH responsive, insoluble in acidic environments, and shows increased absorption in human duodenum explants and *Caenorhabditis elegans* at neutral pH. It is sensitive to glucosidase enzymes, which trigger insulin release. The formulation distributes to the liver in mice and rats after oral administration, promoting a dose-dependent reduction in blood glucose without causing hypoglycemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose without adverse effects. The study demonstrates the potential of this formulation to control blood glucose levels orally without hypoglycemic episodes, addressing the escalating burden of diabetes and its complications.