ABSTRACT
NanoneuromedicinesA major developmental concern is how best to target the CNS while reducing general cytotoxicities. Notably, unique challenges exist for the development of effective nanotherapeutics for neuroscience. These include their ability to cross the BBB and maintain therapeutic drug levels in the CNS. Drugs must be effective at low concentrations and exhibit both low toxicity and low immunogenicity [1]. To surmount these challenges, a number of strategies have been employed in formulation development. Liposomal drugs can cross the BBB. Such a strategy is commonly employed for anti-epileptics, -fungals, -retrovirals, -ischemics and chemotherapeutic agents. Specific targeting moieties are added on the surface to facilitate delivery to sites of action. Micelles, using amphiphilic block polymers that surround noncovalently bound drugs, can also cross the BBB [10]. Polymeric nanoparticles using biodegradable polymers to encapsulate drug(s) or carry it by attaching it to the nanoparticle surface can speed BBB passage by tight junctions, facilitated endocytosis or inhibition of efflux transporters on endothelial cells. Dendrimers can carry drug(s) within their own branching structures and can be modified to enhance penetration into the brain. Macrophages may also be used as drug carriers to deliver nanoparticles across the BBB [11].With the development of nanoparticles also comes concern over potential adverse effects. Special concerns have been raised over their small size, surface charge, molecular composition, surface area, route and duration of administration. This can and often does increase the potential for toxic cellular interactions. Notably nanoparticulate carriers can elicit pro-oxidant and inflammatory properties. Thus, efforts to reduce potential
adverse toxicities have focused on the use of biodegradable and biocompatible polymers that can evade the reticuloendothelial system and better promote nanocarrier drug release [6]. Reduction in dose and dose frequency may be achieved with the addition of cell-specific targeting moieties.
