Over the barrier and through the blood: to CNS delivery we go

Overview

The parenteral route is a critical method of drug administration. It delivers compounds directly into the systemic circulation and bypasses the gastrointestinal tract. This approach is particularly advantageous for drugs that exhibit poor absorption or instability when administered orally.
There are three primary parenteral routes: intravenous (IV), intramuscular (IM), and subcutaneous (SC). The IV route introduces the drug directly into the bloodstream, ensuring immediate action. The IM route...

Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...

Drug distribution in the body is intricately regulated by various physiological barriers that control the passage of substances. These include the capillary endothelial barrier, the blood-brain, blood-cerebrospinal fluid, blood-placental, and blood-testis barriers.
The capillary endothelial barrier allows only smaller molecules below 600 Da (Daltons) to pass through. It also restricts drugs like heparin that are bound to blood components, limiting their movement within the bloodstream.
The...

Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.

Cerebrospinal fluid (CSF) is a colorless liquid that flows around the brain and the spinal cord, playing a vital role in the protection, support, and overall function of the central nervous system (CNS). CSF production, circulation, and absorption are tightly regulated processes essential for the brain and spinal cord to function properly.
CSF Production
CSF is produced mainly in the choroid plexus, a network of capillaries and ependymal cells located within the ventricular system of the brain.