A Focus on Glucose-Mediated Drug Delivery to the Central Nervous System

I. D. Serrano, M. M.B. Ribeiro, M. A.R.B. Castanho

doi:10.2174/138955712799829302

Abstract

Drug delivery to the central nervous system (CNS) is a timely and challenging issue: 95% of the pharmacological drugs cannot be delivered to the brain. This is mainly due to the blood-brain barrier (BBB), a highly selective boundary that hampers the passage of most compounds into the CNS. To overcome this problem, several approaches exist to deliver a therapeutic drug to the brain that takes into account not only the chemical properties of the drug but also the type of transport used at the BBB. One of those strategies is the glucose-mediated drug delivery which will be the focus of the present review. Glucose-mediated drug delivery requires the attachment of glycosyl moieties to a drug and the use of endogenous glucose transporters as a way to circumvent the blood-brain barrier. Glycosylated drugs display improved cell penetrability, enhanced biodistribution, stability and low toxicity. Examples such as glycosylation of ibuprofen and different opioids result in an enhanced central effect and will be discussed.

Keywords: blood-brain barrier, central nervous system, drug delivery, glucose derivatives, glycosylation, cationized albumin, transferrin, Carrier-mediated, hexose, cell membranes, phosphosphorylation