Lecture 3 Barriers to drug delivery

Question 1

Describe drug efflux pumps.

Answer 1

Proteins that actively transport substances like drugs and toxins out of cells, reducing intracellular concentrations. They play a crucial role in the defense mechanism of living cells.

Question 2

What is the role of P-glycoprotein in human cells?

Answer 2

P-glycoprotein, encoded by the MDR1 gene, actively pumps out drugs from cells, limiting their absorption, distribution, and retention. It acts as a protective mechanism against xenobiotics and toxins.

Question 3

How do efflux pump inhibitors work?

Answer 3

Efflux pump inhibitors block the activity of drug efflux pumps, allowing existing drugs to enhance their intracellular concentrations when used in combination.

Question 4

Define combination therapy in the context of drug delivery.

Answer 4

Combination therapy involves combining drugs that are substrates for different efflux pumps or using drugs with different mechanisms of action to overcome drug resistance.

Question 5

What is the purpose of structural modification of drugs in drug delivery?

Answer 5

Structural modification of drugs involves altering their chemical structure to make them less susceptible to efflux pump recognition and expulsion.

Question 6

Describe nanoparticle delivery systems in drug delivery.

Answer 6

Nanoparticle delivery systems can protect drugs from efflux pumps, improve their bioavailability, and increase drug concentration in target cells.

Question 7

How can genetic strategies be used to overcome drug delivery barriers?

Answer 7

Genetic strategies involve downregulating the expression of efflux pump genes using gene-silencing techniques.

Question 8

Explain the concept of personalized medicine approach in drug delivery.

Answer 8

Personalized medicine involves tailoring treatments based on individual patient genetic codes to optimize drug delivery and effectiveness.

Question 9

Describe opsonisation.

Answer 9

opsonisation is a process where opsonins mark an invading entity, making it more susceptible to phagocytosis by phagocytes.

Question 10

Define opsonins.

Answer 10

Opsonins are antibodies or complement proteins that enhance phagocytosis by marking an antigen for ingestion.

Question 11

describe the mechanism by which opsonins enhance phagocytosis?

Answer 11

Opsonins bind to the surface of foreign material, are recognized by phagocytes, and facilitate engulfment, killing, and degradation of the ingested material.

Question 12

What factors influence opsonisation?

Answer 12

Factors such as particle size, surface charge, and surface hydrophilicity affect opsonisation.

Question 13

Describe the properties that affect the route and mechanism of drug absorption through mucosa.

Answer 13

Properties like chemical stability, lipid solubility, aqueous solubility, molecular weight, and pKa influence drug absorption through mucosa.

Question 14

How can lipid solubility of a drug be enhanced?

Answer 14

Lipid solubility can be enhanced by reducing hydrogen bonding groups through esterification or alkylation, or by formulating prodrugs with enhanced permeation properties.

Question 15

Describe the Henderson-Hasselbalch equation.

Answer 15

It is used to calculate the pH of a solution containing a weak acid or base, involving the pKa of the compound and the concentrations of its ionized and unionized forms.

Question 16

What is the distribution coefficient used for in drug delivery?

Answer 16

It applies to ionizable drugs and helps determine how a drug distributes between two immiscible phases, often between water and an organic solvent.

Question 17

How does the pH partition theory impact drug absorption?

Answer 17

It is an approximation that does not consider experimental observations like the large mucosal surface area of the small intestine, long residence time, and limited absorption of ionized forms of drugs.

Question 18

Define bulk transport in drug delivery.

Answer 18

It involves the movement of water from the gut to the blood, carrying water-soluble drug molecules along with it, often facilitated by carriers.

Question 19

Describe the types of drug release mechanisms in drug delivery.

Answer 19

They include immediate release (rapid drug release within 45 minutes) and modified release (controlled release at specific rates, times, or sites for advantages like maintaining therapeutic levels and reducing side effects).