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
What can help limit the rate at which liposomes breakdown and release the drugs inside?
Lipoome residence time in the blood can be extended to many hours to days via the impantation of PEG chains on the liposome surface. Due to this delay in breakdown, the liposme can sequester in other organs (ex. tumours and inflammed tissue)
What are the advantges of liposomes over other particulate systems?
Low toxicity and safety
Large aquoues core helps stabilize the strucutal features of proteins
Ability to control where drug is deposited
PEGylation
What is PEGylation?
In addition to prolonging residence time of liposomes, a drug encapsuled by PEG can also shield it from immune responses.
PEG can also increase drug water solubility
What are the limitations of using liposomes as a drug delivery device?
Poor access to target sites outside the blood circulation (high resistance to liposome penetration through endothelial lining)
Liposomes cannot access cavities like the bladder or peritoneal cavity
What are the different types of controlled release systems for parenteral delivery?
Open loop type: continous infusion with mechanical of osmotic pumps
Closed loop approach/feedback system: Biosensor-pump combination (no human interference)
Review slides 30-35 to examine mechanical and osmotic pumps in controlled drug release
What are the disadvantages of an osmotic pump in the context of controlled release drug delivery systems?
This type of pump has a fixed release rate, which is not always desired (may need pulsatile secretion to better mimic the body’s normal functioning)
What are the disadvantages of a mechanical pump in the context of controlled release drug delivery systems?
- Patient has to collect data to adjust pump rate (requires invasive sampling on a regular basis) + human interference
- Pump could fail (no part is the best part)
- Drug stability
