Drug Delivery Systems Flashcards
What is the definition of drug delivery?
the appropriate administration of drugs through various routes in the body for the purpose of improving health
What are the factors to be considered in a drug delivery system?
drug physicochemical properties
body effects and interactions
improvement of drug effect
patient comfort and well being
What does the magnitude of drug response depend on?
depends upon concentration achieved at site of action:
-dosage
-extent of absorption
-distribution to the site
-rate/extent of elimination
What are the barriers to protein drug delivery?
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
What are the approaches to enhance bioavailability of proteins?
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
What is iontophoresis?
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)
Can iontophoretic delivery devices be worn permanently?
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
What are the reasons drug fail?
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
True or false: you can directly inject a drug into the target site
false
must develop a way to target the drug so that we can provide the drug systematically and have it reach the target
What is targeted drug therapy?
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
What can recent progress of targeted therapy be ascribed to?
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
What is passive targeting?
the natural disposition pattern of the carrier system is utilized for delivery
What is active targeting?
concept where attempts are made to change the device by using “homing principle” to select one tissue or cell type
When do we target drugs?
drugs with high total clearance
increases in rate of elimination of free drug
response sites with small blood flow
What does the fate of particulate carriers depend on?
size
charge
hydrophobicity
presence of homing devices on their surface
What are examples of colloidal particulate carrier systems?
liposomes
LDL
What is the structure of liposomes?
vesicular structures based on phospholipid bilayer surrounding an aqueous core
How can liposome residence time be extended in the blood?
PEG chains are grafted on the surface and stable bilayer structures
-PEG liposomes are able to escape macrophages and are sequestered in other organs
What are the advantages of liposomes over other particulate systems?
low toxicity
large aqueous core
ability to control disposition by changing preparation techniques and bilayer consituents
PEGylation
What is PEGylation?
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
What are the limitations of liposomes?
poor access to target sites outside the blood circulation
high resistance against liposome penetration through endothelial lining
What is an open loop system?
continuous infusion with pumps or osmotically driven
What is a closed loop approach/feedback system?
biosensor-pump combination
encapsulated secretory cells
Describe open loop systems for mechanical pumps type 1.
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
Describe osmotically driven open loop systems.
- incoming water empties the drug containing reservoir
surrounded by a flexible impermeable membrane - release rate depends on characteristics of semi-permeable
membrane and on osmotic differences over this membrane - protein solution must be physically and chemically stable at
body temperature - the protein solution must be compatible with the pump
parts to which it is exposed
What is a limitation of osmotically driven systems?
fixed release rate which is not always desired
not currently used on regular basis in clinics
Describe open loop insulin pumps.
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
What are the disadvantages of open loop insulin pumps?
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
What is the goal of closed loop insulin pumps?
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
What occurs after injection of “standard” liposomes?
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
What are the outcomes on a molecule that has undergone PEGylation?
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
Where should target sites be sought for liposomes?
in the blood circulation (RBCs, lymphocytes, endothelial cells)
True or false: controlled release systems or continuous infusion cannot be used to administer protein therapeutic drugs
false
it can be used to administer protein therapeutic drugs
ex: insulin
What is the aim of rate controlled delivery?
optimize the therapeutic benefit of the drug
What is the rate determining process of osmotic pumps?
influx of water through the external semi-permeable membrane
Why should microencapsulated secretory cells be protected from the body environment?
rejection processes would immediately start of imperfectly matched cell material is used
prevent cells from migrating in different directions
