European Journal of Biomedical and Pharmaceutical Sciences

TARGETED DRUG DELIVERY ACROSS BLOOD-BRAIN-BARRIER EMPLOYING NATURAL NANOCARRIERS

Jaya T. Varkey*

ABSTRACT

The central nervous system (CNS) of the body is protected by blood brain barrier (BBB). BBB is a highly complex structure that precludes the delivery of drugs to the brain, thus preventing the treatment in a number of diseases. One of the more significant reasons for the difficulty in treating brain diseases concerns the problems faced by many drugs when crossing the BBB. The barrier is formed by endothelial cells which are connected to each other at “tight” junctions that create a complete seal between them. Consequently, only lipophilic molecules are able to cross the barrier. Hydrophilic substances, in contrast, are unable to cross the lipid walls unless associated with a specific transporter. The inability of active agents to cross the barrier effectively means that those agents will not accumulate in adequate concentrations unless large doses are administered, doses that can have significant toxic side effects in other tissues. Establishing new therapeutic approaches to the treatment of cerebral diseases such as stroke, Alzheimer’s disease or brain cancers has to address this issue of crossing the BBB. Moreover recent studies evidence the involvement of the BBB and especially the brain endothelial cells in the pathological process for numerous brain diseases suggesting the necessity to develop specific targeting for these cells The efficiency of many drugs is restricted to their potential to reach the site of therapeutic action. In recent years, the use of nanotechnology has been considered as a valuable strategy to achieve drug delivery to the brain and nanoparticles are developed as potential drug carriers. Nanocarriers possess unique features due to their size, can encapsulate therapeutic dose of many drugs and can be functionalized with various ligands for tissue and cell targeting. Lately peptides have been described as potential ligands for achieving endothelial cells and more specifically BBB targeting of nanocarriers. But the biodegradability of these nanocarriers is a serious problem. Many naturally occurring biocompatible materials can be used as nanocarriers. This review is focused on nano drug delivery using biodegradable, nontoxic and inexpensive natural molecules like chitosan, gelatin and PLGA as carriers. Role of nanoparticle size, bulk material chemistry, and surface chemistry in crossing the BBB is also discussed.

Keywords: BBB, drug delivery, biodegradable, nanoparticles.