Dendrimers as Novel Systems for Delivery of Neuropharmaceuticals to the Brain

Sarwar      Beg; Abdus      Samad; M.      I. Alam; Iram      Nazish

doi:10.2174/187152711796235023

Abstract

Most of the newly developed drugs fails to achieve sufficient bioavailability in to brain due to low water solubility and low permeability. Drug delivery systems are one method for achieving entry of molecules to their desired site of action within the body. Dendrimers are the customizable nanopolymers with uniform and well-defined particle size and shape. Dendrimers are of eminent interest for biomedical applications because of their ability to cross cell membranes. This potential pharmaceutical delivery system crosses the blood brain barrier (BBB) and other important target points. The high level of control over the dendritic architecture (size, branching density, surface functionality) make dendrimers ideal carriers in the field of brain drug delivery of anticancer, antiinflammatory, and antimicrobial agents. Examples of dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI) and polyether-copolyester (PEPE), Glyco, PEGylated, peptide and pH dendrimers are of outmost significance. These dendrimers carriy the drug molecules by physical interactions (encapsulation) or through chemical bonding (prodrug approach), while pH sensitive dendrimers are able to deliver drug molecules by alteration of ionic exchange in the brain microenvironment at the tumor site. Techniques employing dendrimers could be especially useful for drugs targeting to Alzheimer's and Prion's diseases. The present review should be of value to scientists who wish to work on the dendrimers for the delivery of molecules into the brain by systemic dosing.

Keywords: Dendrimer, blood-brain barrier, boron neutron capture therapy, brain targeting, PAMAM, VIVA GEL, L-DOPA, Caco-2, Transferrin, PEPE, PPI, Starburst, LRP1, BNCT, CT-MR