Why are liposomes less harmful for your body? And why are they good for the drug itself?
Since they are naturally occurring in the body, you can put them in the blood because it is biocompatible (bio membrane= bilayers made of phospholipids). Also, it reduces toxicity because you’re hiding the drug in the liposome. Hiding the drug in the enzyme also protects it from the environment.
What are examples of drugs encapsulated in liposomes?.
Amphotericin B (ambisome, abelcet), doxorubicin (doxil, myocet).
Name the types of liposome based on their layers.
Multilamellar and unilamellar.
Name of two components of a phospholipid and what they are composed of.
Polar head (contains 1+phosphate groups) and hydrophobic tail (fatty acid chains).
Name the components of a liposome.
Phospholipids, aq. Phase, drug (water or lipid soluble), cholesterol, antioxidant, buffer, NaCl, steryl amine(+) or dicetyl phosphate(-), chelating agents (EDTA).
Phospholipids are also described as ______.
What are two commonly used phospholipids for liposomes?.
Phosphatidylcholines (lecithins), such as egg and soya lecithin.
Why are phosphatidylcholines commonly used?.
Lower cost, chemical inertness, and lack of net charge.
Can a lysolipid (one tail) form a liposome in water?.
No, makes a micelle.
What is a commonly used antioxidant for liposomes?.
Name all the antioxidants used for liposomes?.
A-tocopherol and hydroxytoluene (BHT).
What is the role of cholesterol?.
Used to make a liposome more rigid and less leaky; imparts stability.
What two factors indicate good physical stability of a liposome?.
Size is small and remains the same as well as drug retention.
What two reactions can liposomes undergo?.
Hydrolysis and oxidation.
What are two components that determine liposome chemical stability?.
Drug degradation and the chemical rxn that they undergo (hydrolysis and oxidation).
What parts of the liposome can undergo degredative reactions and what rxns can they undergo?
Phospholipids (hydrolysis), unsaturated fatty acids (oxidative rxns) and cholesterol (oxidation).
In vivo behavior of liposomes depends on what factors.
Size, charge and lipid composition.
What happens when liposomes don’t have cholesterol?
What happens when you inject liposomes intraveneously?
Are cleared by phagocytic cells of the RES.
What is another name for RES?
Mononuclear phagocytic system (MPS).
What two organs are part of the RES?
Liver and spleen.
What size liposomes are cleared faster by the RES system?
Large is cleared faster than small.
Explain the fate of liposomes injected IM or SC.
They are slowly dispersed from the injection site, absorbed into the lympathic system, then are either sequestered by lymphatic phagocytes or return to blood stream where they’re sequestered by RES.
What substance do you use to make a “stealth liposomes.”
Polymer: Polyethylene glycol (PEG).
What is the mechanism of PEG to protect the liposomes?
Provides a hydrophilic barrier to prevent the binding of opsonins, reducing the clearance from RES. Improves the half lives of liposomes.
What is another name for drug targeting?
Site specific drug delivery.
What are the two types of drug targeting?
Passive and active.
What is the difference b/w passive and active drug targeting?
Passive drug delivery follows its’ fate, while active transport can be manipulated by using a monoclonal antibody.
What is amphotericin B used for? What is an extreme side effect of it?
Antifungal antibiotic. Neurotoxicity.
What two drugs contain Amphotericin B?
Abelcet and AmBisome.
What two phospholipids is Abelcet made of?
Dimyristoylphosphatidylglycerol (DMPG) and dimyristolphosphatidylcholine (DMPC).
What is the ratio of DMPC to DMPG. What drug is it in?
7:3 molar ratio. Abelcet.
What is the drug (amphotericin B) to lipid molar ratio in Ambelcet?
What is the dosage form of Abelcet?
What color is Abelcet?
pH of Abelcet?
What 3 organs does a majority of Amphotericin B distribute to?
Spleen, liver and lung.
Why is the incidence of nephrotoxicity lower for Abelcet (at a higher dose 5mg/kg/day) compared to conventional amphotericin B (0.7mg/kg/day)?
Abelcet is inside a liposome, which means the drug is mainly acting on target site.
What is the daily recommended dosage for adults and children when abelcet is given as a single infusion?
Rate of IV infusion rate for Abelcet?
What temperature should Abelcet be stored @?
T/F Abelcet should be protected from light and NOT frozen.
How long can abelcet and 5% dextrose be stored for?
48 hours @ 2-8oC and 6hr @ room temp.
T/F Ambisome is a lyophilized product.
What has to be done to AmBisome before administration?
Reconstituted with sterile water for injection.
T/F AmBisome is a true single bilayer liposomal drug delivery system.
If a patient is infused with AmBisome experiences discomfort, what can you do? Increase duration of infusion.
Storage conditions of AmBisome before and after reconstitution?
Before= in fridge @ 2-8oC. After= can be stored up to 24 hours @ 2-8oC.
Should you freeze AmBisome?
T/F. AmBisome contains preservatives or bacteriostatic agents.
What type of antibiotic is Daunorubicin? And what is it used for?
Anthracycline antibiotic. It is an anticancer drug, specifically for advanced HIV-associated Kaposi’s sarcoma.
What is the trade name for Daunorubicin Citrate?
What is the trade name for Doxorubicin?
What is the generic name for Doxil?
T/F Doxil is not pegylated.
What is the advantage of DaunoXome?
Storage conditions of DaunoXome?
Store in fridge @ 2-8oC, don’t freeze and protect from light.
What two drugs require protection from light?
Abelcet and DaunoXome.
What type of antibiotic is Doxorubicin?
A cytotoxic anthracycline antibiotic.
What is unique about Doxil?
It’s a ninja. It’s got pegylated stealth technology.
What color is Doxil?
What is the generic name for Doxil?
Which drug incorporates Ammonium sulfate? What is its’ purpose?
Doxil. It complexes with doxorubicin to help keep the drug inside.
Why shouldn’t you administer a bolus injection or undiluted solution of liposomes? Risk of inflammatory response.
What kind of tissues does Doxil preferentially distribute to?
Compromised or chaotic vasculature such as tumors.
What is the name of the mechanism by which Doxil enters through gaps/defects in tumor blood vessels.
What is extravastion and which cytotoxic anthracycline drug uses this mechanism?
It is ability to travel through gaps or defects in blood vessels. Doxil.
T/F. Doxil extravasates in blood vessels undergoing angiogenesis.
Why do you need to dilute Doxil in 250ml of 5% dextrose even though sucrose is already added?
To maintain isotonicity in a larger volume.
Storage conditions of Doxil?.
Refrigerate @ 2-8oC. Avoid freezing.
Is short-term freezing (less than a month) ok for Doxil?