Delivery of Sulfonylurea Anti-hyperglycemic Drugs across Phospholipid Membranes

The mechanism by which Sulfonylurea drugs cross the phospholipid membranes is not fully understood. A model has previously been proposed for the transport of long chain fatty acids which cross the phospholipid membrane by "free diffusion" mechanism. Fluorimetric assays have demonstrated that Sulfonylureas also cross the Phospholipid membrane by "free diffusion" to enter the lumen of small unilamellar vesicles (SUVs). Transport of Sulfonylureas causes a drop in pH inside the vesicles which results in a drop in fluorescence intensity of the trapped Pyranin dye in SUVs. This model is physiologically significant since ATP-sensitive K+ ion channels serve as Sulfonylurea receptors in ?-cells of the Islets of Langerhans and excitable cells such as heart and muscle cells along with dopaminergic neurons. To bind to the receptor, the molecules are required to cross the phospholipid bilayer either by free diffusion or with the help of transport proteins. In the absence of any known transport proteins, the proposed mechanism represents a viable model to explain the delivery of these compounds to living cells.