Drug Delivery Systems

Question 1

What is the definition of drug delivery?

Answer 1

the appropriate administration of drugs through various routes in the body for the purpose of improving health

Question 2

What are the factors to be considered in a drug delivery system?

Answer 2

drug physicochemical properties
body effects and interactions
improvement of drug effect
patient comfort and well being

Question 3

What does the magnitude of drug response depend on?

Answer 3

depends upon concentration achieved at site of action:
-dosage
-extent of absorption
-distribution to the site
-rate/extent of elimination

Question 4

What are the barriers to protein drug delivery?

Answer 4

enzymatic barrier
-limits absorption of protein drugs from GI tract
intestinal epithelial barrier:
-involved in the transport of protein drugs across epithelium
capillary endothelial barrier:
-involved in transport of protein drugs across the capillary
endothelium
blood brain barrier:
-involved in transport of protein drugs to brain compartment

Question 5

What are the approaches to enhance bioavailability of proteins?

Answer 5

enhance permeability of absorption barrier
-add fatty acids, bile salts, esters, detergents
-through iontophoresis
-by using liposomes
decrease peptidase activity at the site of absorption and along the absorption route
-enhance resistance against degradation

Question 6

What is iontophoresis?

Answer 6

a transdermal electrical current is induced by positioning two electrodes on different places on the skin
current induces a migration of ionized molecules through the skin
+ve charged drug on anode (active electrode)

Question 7

Can iontophoretic delivery devices be worn permanently?

Answer 7

can be worn permanently and only switched on over the desired periods of time
stimulating pulsatile secretion of endogenous hormones such as growth hormone and insulin

Question 8

What are the reasons drug fail?

Answer 8

active compound never reaches the target site
-rapidly eliminated or inactivated
molecules do not enter cells easily
-high MW or hydrophilic
small fraction of drug reaches the target site

Question 9

True or false: you can directly inject a drug into the target site

Answer 9

false
must develop a way to target the drug so that we can provide the drug systematically and have it reach the target

Question 10

What is targeted drug therapy?

Answer 10

should maximize therapeutic effect and minimize toxicity
-by specific delivery of active compound at its site of action
-keep it there until it has been inactivated and detoxified

Question 11

What can recent progress of targeted therapy be ascribed to?

Answer 11

nature of physiological and anatomical barriers that hinder easy access to target sites was revealed
new insight into pathophysiology of disease at cellular and molecular level (including specific receptors and homing devices)
rapidly growing number of technological options

Question 12

What is passive targeting?

Answer 12

the natural disposition pattern of the carrier system is utilized for delivery

Question 13

What is active targeting?

Answer 13

concept where attempts are made to change the device by using “homing principle” to select one tissue or cell type

Question 14

When do we target drugs?

Answer 14

drugs with high total clearance
increases in rate of elimination of free drug
response sites with small blood flow

Question 15

What does the fate of particulate carriers depend on?

Answer 15

size
charge
hydrophobicity
presence of homing devices on their surface

Question 16

What are examples of colloidal particulate carrier systems?

Answer 16

liposomes
LDL

Question 17

What is the structure of liposomes?

Answer 17

vesicular structures based on phospholipid bilayer surrounding an aqueous core

Question 18

How can liposome residence time be extended in the blood?

Answer 18

PEG chains are grafted on the surface and stable bilayer structures
-PEG liposomes are able to escape macrophages and are sequestered in other organs

Question 19

What are the advantages of liposomes over other particulate systems?

Answer 19

low toxicity
large aqueous core
ability to control disposition by changing preparation techniques and bilayer consituents
PEGylation

Question 20

What is PEGylation?

Answer 20

covalently attaching PEG to another molecule
drug encapsulated with PEG can prevent immune response
increases water solubility of drug
can add targeting molecules to the PEGylated drug

Question 21

What are the limitations of liposomes?

Answer 21

poor access to target sites outside the blood circulation
high resistance against liposome penetration through endothelial lining

Question 22

What is an open loop system?

Answer 22

continuous infusion with pumps or osmotically driven

Question 23

What is a closed loop approach/feedback system?

Answer 23

biosensor-pump combination
encapsulated secretory cells

Question 24

Describe open loop systems for mechanical pumps type 1.

Answer 24

pulsatile or variable-rate delivery is the desired mode of input for a number of these drugs
pumps should provide flexible input rate
mechanically driven pumps are common tools to administer drugs IV in hospital

Question 25

Describe osmotically driven open loop systems.

Answer 25

1. incoming water empties the drug containing reservoir
   surrounded by a flexible impermeable membrane
2. release rate depends on characteristics of semi-permeable
   membrane and on osmotic differences over this membrane
3. protein solution must be physically and chemically stable at
   body temperature
4. the protein solution must be compatible with the pump
   parts to which it is exposed

Question 26

What is a limitation of osmotically driven systems?

Answer 26

fixed release rate which is not always desired
not currently used on regular basis in clinics

Question 27

Describe open loop insulin pumps.

Answer 27

insulin administration by continuous SQ infusion and monitoring of glucose levels
delivers basal infusion and meal-time bolus doses into abdominal wall
insulin delivered through soft tube

Question 28

What are the disadvantages of open loop insulin pumps?

Answer 28

patient has to collect data and adjust pump rate
invasive sampling on a regular basis followed by calculation of required input rate
pump may fail
drug stability

Question 29

What is the goal of closed loop insulin pumps?

Answer 29

to develop a system where the regulation of insulin injections are directly based on current blood readings
does not require patient to be involved
readings must be in real-time
regulation controlled internally

Question 30

What occurs after injection of “standard” liposomes?

Answer 30

stay in blood circulation only for a short time
taken up by macrophages in the liver and spleen, or degraded by exchange of bilayer constituents with blood constituents

Question 31

What are the outcomes on a molecule that has undergone PEGylation?

Answer 31

polymer formed is non-antigenic, non-toxic, non-immunogenic, and highly water soluble
increases half-life of the drug and reduces dose frequency by preventing renal excretion

Question 32

Where should target sites be sought for liposomes?

Answer 32

in the blood circulation (RBCs, lymphocytes, endothelial cells)

Question 33

True or false: controlled release systems or continuous infusion cannot be used to administer protein therapeutic drugs

Answer 33

false
it can be used to administer protein therapeutic drugs
ex: insulin

Question 34

What is the aim of rate controlled delivery?

Answer 34

optimize the therapeutic benefit of the drug

Question 35

What is the rate determining process of osmotic pumps?

Answer 35

influx of water through the external semi-permeable membrane

Question 36

Why should microencapsulated secretory cells be protected from the body environment?

Answer 36

rejection processes would immediately start of imperfectly matched cell material is used
prevent cells from migrating in different directions