<P> Drug delivery to the brain is the process of passing therapeutically active molecules across the blood--brain barrier for the purpose of treating brain maladies . This is a complex process that must take into account the complex anatomy of the brain as well as the restrictions imposed by the special junctions of the blood--brain barrier . </P> <P> The blood--brain barrier is formed by special tight junctions between the epithelial cells that surround the brain tissue . All tissue is separated by this layer of epithelial cells, however only the brain epithelial cells have these tight junctions that do not allow larger molecules to pass between them . The structure of these tight junctions was first determined in the 1960s by Tom Reese, Morris Kranovsky and Milton Brightman . These tight junctions are formed through the tight apposition of the endothelial cells with one another . Furthermore, astrocytic, "end feet" "the terminal regions of the astrocytic processes surround the outside of the capillary endothelial cell". The astrocytes are glial cells that are restricted to the brain and spinal cord that work to maintain an appropriate environment for neural signaling . The connection between these glial and endothelial cells is not very well known but it "may reflect an influence of the astrocytes on the formation and the maintenance of the blood--brain barrier . </P> <P> The main function of the blood--brain barrier is to protect the brain and keep it isolated from harmful toxins that are potentially in the blood stream . It accomplishes this because of its structure, as is usual in the body that structure defines its function . The tight junctions between the endothelial cells prevent large molecules as well as many ions from passing between the junction spaces . This forces molecules to go through the endothelial cells in order to enter the brain tissue, meaning that they must pass through the cell membranes of the endothelial cells . Because of this, the only molecules that are easily able to transverse the blood--brain barrier are ones that are very lipid - soluble . These are not the only molecules that can transverse the blood--brain barrier; glucose, oxygen and carbon dioxide are not lipid - soluble but are actively transported across the barrier, to support normal cellular function of the brain . The fact that molecules have to fully transverse the endothelial cells makes them a perfect barricade to unspecified particles from entering the brain, working to protect the brain at all costs . Also, because most molecules are transported across the barrier, it does a very effective job of maintaining homeostasis for the most vital organ of the human body . </P> <P> Because of the difficulty for drugs to pass through the blood--brain barrier, a study was conducted to determine the factors that influence a compound's ability to transverse the blood--brain barrier . In this study, they examined several different factors to investigate diffusion across the blood--brain barrier . They used lipophilicity, Gibbs Adsorption Isotherm, a Co CMC Plot, and the surface area of the drug to water and air . They began by looking at compounds whose blood--brain permeability was known and labeled them either CNS+ or CNS - for compounds that easily transverse the barrier and those that did not . They then set out to analyze the above factors to determine what is necessary to transverse the blood--brain barrier . What they found was a little surprising; lipophilicity is not the leading characteristic for a drug to pass through the barrier . This is surprising because one would think that the most effective way to make a drug move through a lipophilic barrier is to increase its lipophilicity, it turns out that it is a complex function of all of these characteristics that makes a drug able to pass through the blood--brain barrier . The study found that barrier permittivity is "based on the measurement of the surface activity and as such takes into account the molecular properties of both hydrophobic and charged residues of the molecule of interest ." They found that there is not a simple answer to what compounds transverse the blood--brain barrier and what does not . Rather, it is based on the complex analysis of the surface activity of the molecule as well as relative size . </P>

Can lipid soluble drugs cross blood brain barrier