Drug Delivery Systems Flashcards
What factors are considered when creating drug delivery systems?
Drug physiochemical properties
Body effects and interactions
Improvement of drug effect
Patient comfort and well being
What are some factors that affect the magnitude of drug response?
Dosage and ADME
What are the two types of drug delivery systems?
Conventional (Enteral, Parenteral, and Other)
Controlled (Sustained, Extended, Site-specific, and pulsatile)
What are some barriers to biologic/protein drug delivery in the body?
Enzymatic barrier: Limited absorption of protein drugs from GI
Intestinal epithelial barrier: Involved in protein transport across the intestinal epithelium
Capillary endothelial barrier: Involve in protein transport across the capillary endothelium
Blood Brain Barrier: Involved in protein transport to brain compartment
What are some approaches to enhance bioavailability of biologics/proteins by modifying host factors?
- Increase the permeability of the absorption barrier. This is done via iontophoresis and liposomes (addition of FFA/phospholipids, bile salts, etc.)
- Decrease peptidase activity at the site of absorption and along the ‘absorption route’. (Protease inhibitors can help reduce breakdown of product)
What is iontophoresis?
A transdermal electrical current is induced by positioning two electrodes on different places on the skin.
The current induces the migration of ionized molecules through the skin
Delivery of depends on the current (pulsed/direct), pH, ionic strength, charge on protein, and temperature
What is the utility of iontophoresis?
This form of delievery offers the ability to conduct pulsed delivery of product.
The devue can be worn permanently and can be switched on and off in a pulsatile manner. This results in pulsatile delievrythat can mimic the pulsatile secretion of endogenous hormones like hGH and insulin
Why do biologic drugs fail?
- The active compound does not reach the target site (eliminated quickly or metabolicallu inactivated)
- Molecules do not enter the cells (high MW or hydrohillic nature)
- Small fracton of the drug reaches the target site (need to focus distribution to target sites, usually cannot directly inject into the target, need to be creative and employ what we know about anatomy, chemistry, and pathology)
What is the purpose of targeted drug therapy?
Targeted drug delivery should maximize teh therapeutic effect and avoid toxic effecsts elsewhere
What are homing devices in terms of targeted drug therapy?
Ex. An antibody that is tailored to bind at the target site is attached to the drug. The drug will follow the antibody to the target site.
The antibody is the homing device
What is passive targeting?
This is the natural dispositon pattern of the carrier system is utilized for drug delivery.
ex. macrophages picking up drug and taking them to the liver and spleen as a part of their normal function
Drug is near target
What is active targeting?
Attempts are made to change the device by using the “homing principle” to select one particular tissue or cell type
Drug is attached to target (more intimate vs. passive targeting)
When should we use drug targeting techniques?
- drugs with high clearance rates
- Increases in the rate of elimination of free drug
- Target sites with relatively small blood flow
What determines where our biologic product reaches?
Size
Charge
Surface hydrophobicity
Prescense fo homing devices on their surfaces
What type of drug targeting do liposomes use?
Liposomes with drug attached are taken up by macrophages in the liver and spleen. If the drug was intended to have its effect on the liver and spleem, this was passive targeting
