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. Transmembrane proteins, including receptors, ion channels, structural anchors, and transporters, intersperse these bilayers and conduct various cellular activities.
The translocation of drugs across these cellular barriers hinges primarily on passive or active transport mechanisms. Passive diffusion is the most prevalent, enabling drugs to move along their concentration gradient and permeate the cell membrane autonomously or with a transporter's assistance. Such movement of drugs via transporters along their concentration gradient is called facilitated diffusion. Some drugs exploit the paracellular pathway, crossing the intercellular gap.
In contrast, active transport encompasses drugs moving against their concentration gradient, facilitated by ATP-powered transporters. Understanding these transport mechanisms is crucial for successful drug delivery and thereby influences the therapeutic efficacy of pharmacological treatments.
From Chapter 3:
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