MOVEMENT ACROSS BIOLOGICAL MEMBRANES

 

 Drug permeation is defined as the process by which drug crosses the biological membrane. Broadly divided into -Transcellular and Paracellular. Mostly drugs use the transcellular pathway. Transcellular pathway is further divide into simple diffusion and facilitated diffusion.

DIFFUSION is the process by which molecules move along the concentration gradient. Movement occurs through kinetic energy of the molecules. Since no energy is involved it is referred to as passive diffusion.

Net rate of permeation = P * SA * (Cu1- Cu2)

where P - permeability P (micrometer/min)

          SA - surface area

          (Cu1- Cu2) - concentration difference

Major properties that affect the passive diffusion of a drug : Size, Lipophilicity and Charge

These major factors such as size and lipophilicity is considered to play a major role in BBB . Blood brain barrier exists because of tight junctions between the endothelial wallls and the highly resistant glial cells surrounding them.

Charge carried by a particular drug also contributes to drug permeation supported by the pH-partition Hypothesis. Accordingly, only unionized nonpolar drug can permeate the membrane and at steady state concentrations unionized species are equal on both sides of the membrane.

Considering these properties of the drug different membranes also have their own inherent properties such as being more leaky or having tight junctions that ultimately affects the drug permeation

CARRIER - MEDIATED TRANSPORT requires the help of transporters for drug movement. 

 1.Passive facilitated diffusion also called as Equilibrating transporters. Bidirectional process but  does not change at equilibrium.

Eg: ENT 1 & 2 transporters for movement of nucleosides

2.Active transport also called concentrating transporters. These transporters require ATP for moving across the concentration gradient. Further classified into Influx or Efflux transporters.

Eg: MDRI(Multiple drug resistant receptor) is a P- glycoprotein which is an ATP-dependent efflux transporter which is held responsible for the efflux of drug molecules from the cancer cells making them more resistant to drugs.

      OATP-C  is an organic anion Infux  transporter for Benzylpenicillin 

Also classified as PRIMARY ACTIVE TRANSPORTERS  eg: Na-K ATPase

                             SECONDARY ACTIVE TRANSPORTERS eg: antiport and symport 

PARACELLULAR TRANSPORT transport occurring between cells through an intercellular shunt pathway 

Eg: Aquaporins which help more polar drug molecules to pass through

PINOCYTOSIS(pino means to drink) is the uptake of fluids along with dissolved molecules by cells

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