Lecture 21 Drug Delivery Systems

Question 1

What are drug delivery systems / what is their purpose?

Answer 1

These are devices or formulations that aim to deliver drugs to specific sites of the body through controlled delivery and release.

Question 2

Why are DDS needed?

Answer 2

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)

Question 3

What are the ideal features of a DDS

Answer 3

Controlled released
Controlled delivery
Ease of use
Low immunogenicity
Non-toxic

Question 4

What are the main types of DDS?

Answer 4

Oral (controlled release tablet)

Inhaled (metered dose inhalers)

Skin (transdermal patches)

Parental (liposomes / micelles)

Question 5

What are some of the issues with oral formulations?

What are some Benefits?

Answer 5

Bioavailability (absorption / dissolution)
First pass metabolism
Acidity of stomach

Little allergic of hypersensitivity reaction to DDS.

Question 6

What are some oral formulations for DDS?

Answer 6

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.

Question 7

Describe Inhalation devices as a DDS.

Answer 7

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.

Question 8

What are some examples of inhalation devices as DDSs?

Answer 8

Metered-dose inhalers are pressurized or aerosolized.

Disk inhalers, turbuhaler, powder inhalers are non-pressurized / powder.

Question 9

What condition are inhalation devices commonly used for?

Answer 9

Asthma, other airway and lung conditions.

Previously inhaled insulin.

Question 10

Describe DDS applied to the skin in terms of Pros and Cons.

Answer 10

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

Question 11

Describe examples of transdermal DDSs.

Answer 11

Nicotine patch: can be membrane controlled release or non-membrane controlled release.

Estrogen patch: birth control due to constant release of estrogen.

Question 12

Describe parenteral DDSs.

Answer 12

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.

Question 13

Describe the general structure of a liposome.

Answer 13

Hydrophilic core, phospholipid bilayer/membrane

Question 14

Describe the general structure of a micelle.

Answer 14

Lipophilic core surrounded by phospholipid monolayer / outer shell.

Question 15

What are the four types of liposomes and their features? Which are actively or passively targeted?

Answer 15

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?)

Question 16

What are common side effects of conventional anti-cancer drugs?

Answer 16

myelosuppresion (suppress immune system)

alopecia (loss of hair)

stomatitis (inflammation around openings in body)

nausea and vomiting (cisplatin)

neurotoxicity (vincristine)

cardiotoxicity (doxorubicin)

Question 17

What helps to make conventional anticancer drugs induce side effects?

Answer 17

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.

Question 18

What are some pros and cons of liposomes as a DDS?

Answer 18

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.

Question 19

How role does pharmacokinetics play in liposomal DDS?

Answer 19

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.

Question 20

What is the EPR effect?

Answer 20

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.

Question 21

How do liposomes take advantage of the EPR effect?

Answer 21

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.

Question 22

What are thermal sensitive liposomes?

Answer 22

Localized application of heat will increase the passive targeting of liposomes. This is especially useful with surface tumours.

Question 23

How does the portion of an antibody attached as a targettor for a piosome affect its clearance? (according to the discussed study)

Answer 23

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.