Lecture 21 Drug Delivery Systems Flashcards
What are drug delivery systems / what is their purpose?
These are devices or formulations that aim to deliver drugs to specific sites of the body through controlled delivery and release.
Why are DDS needed?
These increase ease of administration, compliance, deposition at specific sites (which decreases adverse side effects, toxicity and increases therapeutic activity), and circumvent formulation issues (like liphophilicity / aqueous administration)
What are the ideal features of a DDS
Controlled released Controlled delivery Ease of use Low immunogenicity Non-toxic
What are the main types of DDS?
Oral (controlled release tablet)
Inhaled (metered dose inhalers)
Skin (transdermal patches)
Parental (liposomes / micelles)
What are some of the issues with oral formulations?
What are some Benefits?
Bioavailability (absorption / dissolution)
First pass metabolism
Acidity of stomach
Little allergic of hypersensitivity reaction to DDS.
What are some oral formulations for DDS?
Extended release or sustained release (release rate dependent on concentration)
Controlled release (release rate not concentration dependent) These maintain a more constant level of drug than sustained release.
Describe Inhalation devices as a DDS.
These are mostly used for delivery of drugs of the resp. tract although some can be for systemic effect.
Drug is deposited in the lungs.
Deposition of particles along respiratory tract depends on size, density, and surface properties of the particles.
Larger particles tend to deposit further up the airway and denser items further down.
What are some examples of inhalation devices as DDSs?
Metered-dose inhalers are pressurized or aerosolized.
Disk inhalers, turbuhaler, powder inhalers are non-pressurized / powder.
What condition are inhalation devices commonly used for?
Asthma, other airway and lung conditions.
Previously inhaled insulin.
Describe DDS applied to the skin in terms of Pros and Cons.
These escape first pass metabolism
Can result in continuous release of drug
Easy administration and removal
Risk of dose dumping (rapid release)
Risk of local irritation / allergy
Describe examples of transdermal DDSs.
Nicotine patch: can be membrane controlled release or non-membrane controlled release.
Estrogen patch: birth control due to constant release of estrogen.
Describe parenteral DDSs.
These include liposomes, micelles, (nanoparticles) ligand-drug conjugates, polymer-drug conjugates.
These are mostly used for delivery of toxic drugs like chemotherapeutics, cancer vaccines, and antifungals.
Describe the general structure of a liposome.
Hydrophilic core, phospholipid bilayer/membrane
Describe the general structure of a micelle.
Lipophilic core surrounded by phospholipid monolayer / outer shell.
What are the four types of liposomes and their features? Which are actively or passively targeted?
Conventional: just bilayer (passive / non targeting)
Stealth: peg attached to polar head of phospholipid. Peg on outside and inside of liposome acts to creat a water shell which protects them from the immune system / detection. (passive targeting)
Targeted: have ligand or Ab attached to Peg on surface of liposomal membrane for active targeting. (active targeting)
Cationic: have positive charges on surfaces; used to deliver RNA commonly. (passive?)
What are common side effects of conventional anti-cancer drugs?
myelosuppresion (suppress immune system)
alopecia (loss of hair)
stomatitis (inflammation around openings in body)
nausea and vomiting (cisplatin)
neurotoxicity (vincristine)
cardiotoxicity (doxorubicin)
What helps to make conventional anticancer drugs induce side effects?
Lack of specificity.
Cytotoxicity against rapidly dividing cells
Large volumes of distribution (drug distributes into normal tissue to a higher degree) resulting in a higher dose needed to get enough drug to the cancer cell.
What are some pros and cons of liposomes as a DDS?
reduced exposure of normal cells to cytotoxic drugs.
Reduced clearance of drug, lower dose needed as more gets to target area.
Hand-foot syndrome is a problem where liposomes pool in the extremities where there are higher pressures (more leaky capillaries allow liposomes to escape here).
liposomes (components/ drug) may induce immunogenic reaction.
How role does pharmacokinetics play in liposomal DDS?
The pharmacokinetics of a drug is dependent on the nature of the carrier and the method of encapsulation (how tightly its bound)
Encapsulated drug assumes PK of liposomes but once released it has the same PK as free drug.
What is the EPR effect?
Tumors result in an enhanced permeability and retention effect. Tumour cells signal for blood vessels to grow, more nutrients, malformed capillaries, looser endothelial cells, not as many tight auctions, gaps between endothelial cells. Also, poor lymphatic drainage.
How do liposomes take advantage of the EPR effect?
At solid tumors, there is more gaps in the endothelial cells due to the EPR effect. Liposomes can more easily exit through these caps into the tumour. There is less lymphatic drainage so liposomes sit around the interstitial spaces of solid tumours and release their payload more preferentially than in other areas.
What are thermal sensitive liposomes?
Localized application of heat will increase the passive targeting of liposomes. This is especially useful with surface tumours.
How does the portion of an antibody attached as a targettor for a piosome affect its clearance? (according to the discussed study)
Having an the Fab or scFv portion of an antibody attached to a liposome increases its half life over whole antibody attachment and compares to the half life of stealth liposomes. This is due to a reduction in Fc-mediated uptake and destruction by phagocytic cells.
