Nano and biotech drugs Flashcards by Astan Kamissoko

Which of the following is NOT considered a form of nanomedicine?
a. Sirolimus nanocrystal
b. Paclitaxel nanoparticles
c. Spironolactone suspension
d. Doxorubicin liposomes
e. All of the above are nanomedicine

c. Spironolactone suspension

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Which of the following is TRUE about Tricor?
a. It consists of drug crystals of fenofibrate of about 100 mm size
b. It is a drug with high water-solubility
c. It is a typical example of new formulation of a BCS Class I drug
d. Its bioavailability is less dependent on taking with food than original fenofibrate
e. It is prepared by lyophilization

d. Its bioavailability is less dependent on taking with food than original fenofibrate

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Which of the following is the other name(s) of Abraxane? Choose the BEST answer.
a. Nab-paclitaxel
b. Solvent-free paclitaxel
c. Taxol
d. A and B are both correct
e. A, B and C are all correct

d. A and B are both correct

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Which of the following refers to spherical vesicles made of phospholipid bilayers?
a. Liposomes
b. Lipid nanoparticles
c. Quantum dots
d. Micelles
e. Emulsion

a. Liposomes

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Which of the following ingredients in a liposomal formulation helps to physically stabilize the
bilayer structure (i.e. to “harden” the liposome)?
a. Tocopherol
b. Hydrogenated soy phophatidylcholine
c. Span 20
d. Distearolyphophatidyl glycerol
e. Cholesterol

e. Cholesterol

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A drug X with high Vd (volume of distribution) and short plasma t1/2 (half-life) is reformulated
as liposomal product. The Vd is substantially reduced and t1/2 prolonged. What has happened
according to what I mentioned in class?
2
a. Drug X in liposomes becomes much more quickly metabolized
b. Drug X in liposomes is getting cleared by the immune system
c. Drug X in liposomes stays in circulation much longer instead of binding to peripheral
tissues
d. Drug X in liposomes now distribute to the peripheral tissues more extensively than
before
e. Drug X in liposomes must have trapped in certain organs

c. Drug X in liposomes stays in circulation much longer instead of binding to peripheral
tissues

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Which of the following is FALSE comparing Fungisome (the new liposomal formulation) with
Fungizone (free drug)?
a. Fungisome penetrates into the brain better
b. Fungisome can be used at higher dose per day than Fungizone
c. Fungisome causes more toxicity in general than Fungizone
d. Fungisome is likely more expensive
e. The drug delivered by fungisome stays in systemic circulation longer

c. Fungisome causes more toxicity in general than Fungizone

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Which of the following is NOT a common advantage of nanomedicine?
a. Allow targeted delivery if properly tagged with targeting ligands
b. No risk of flocculation and coalescence
c. May sometimes improve pharmacokinetics
d. Potentially enter inside cells for drug trafficking effect
e. Can sometimes achieve solvent- or surfactant free drug solubilization

b. No risk of flocculation and coalescence

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Which of the following excipients of a Doxil (liposome formulation of doxorubicin) allows the
liposomes to stay longer in the circulation without being eliminated by immune system?
a. mPEG -distearolyphophatidyl-glycerol
b. Soy phosphatidylcholine
c. Cholesterol
d. α-Tocopherol
e. water for injection

a. mPEG -distearolyphophatidyl-glycerol

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Which of the following is/are TRUE about Abraxane? Please choose the BEST answer?
a. Reconstitution is achieved by injecting the diluent onto the wall of the vial and not directly to
the drug
b. Reconstitution needs to be quickly done at bedside by mixing the diluent with shaking
c. If any foaming or clumping is observed, discard the product right away
d. A and B are both correct
e. A, B and C are all correct

a. Reconstitution is achieved by injecting the diluent onto the wall of the vial and not directly to
the drug

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If a nanocarrier is modified with ligands such as monoclonal antibodies to increase its
specificity for a particular tissue or organ, this is known as ____________
a. Targeted delivery
b. Drug solubilization
c. Drug trafficking
d. Stealth delivery
e. Controlled drug release

a. Targeted delivery

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A rDNA technology product is
a. a peptide or protein
b. a DNA
c. a RNA
d. a small molecule
e. an antisense macromolecule

a. a peptide or protein

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According to what I said in lecture, which of the following molecules is LEAST likely to trigger
an immune response via immunoglobulins?
a. Cholesterol in cell membrane
b. Protein units of the sheath of virus
c. Polysaccharide units on the cell wall of micro-organism
d. Toxins released from bacteria
e. High molecular weight glycoproteins extracted from goat milk

a. Cholesterol in cell membrane

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Which of the following is NOT a biotechnology product?
a. Glucagon-like peptides
b. Glucagon
c. Human growth hormone
d. Aspirin
e. Calcitonin

d. Aspirin

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Which of the following is FALSE about biotechnology drug products?
a. Often “mechanism driven” targeting a specific pathway
b. May be related to pharmacogenomics
c. Easy to develop generic drugs
d. Often quite potent
e. Often considered biologics

c. Easy to develop generic drugs

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Which of the following is/are the potential disadvantages of biotechnology products? Please
choose the BEST answer.
a. High risk of triggering immune responses
b. Highly specific therapeutic activity may not be good for some diseases
c. Limited to oral dosage forms
d. A and B are both correct
e. A, B and C are all correct

d. A and B are both correct

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Which of the following is NOT a factor that normally affects whether a recombinant DNA
product dissolves in an aqueous diluent or not?
4
a. DNAase concentration in the diluent
b. pH of the diluent
c. Ionic strength of the diluent
d. Molecular weight of the product
e. Amino acid composition of the product

a. DNAase concentration in the diluent

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Which of the following peptides has LOWEST water solubility?
a. Contain 4 amino acid units
b. Contain 15% of hydrophobic amino acid and 35% of ionizable amino acid
c. Contain mostly of serine, glutamate and aspartate
d. Contain 50% of tryptophan and phenylalanine plus mostly other neutral amino acids
e. Contain 50% of tryptophan and phenylalanine plus mostly arginine and lysine

d. Contain 50% of tryptophan and phenylalanine plus mostly other neutral amino acids

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Many protein drugs may precipitate in the presence of high concentration of oppositely charged
ions. This is known as ________________
a. Salting out
b. Chelation
c. Creaming
d. Ostrich ripening
e. Ionic repulsion

a. Salting out

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Replacing the Fc portion of monoclonal antibody generated from mice with human Fc (i.e. to
“humanize”) is intended to
a. Increase specificity of the antibody
b. Reduce undesirable immune response against the antibody
c. Reduce the cost of production
d. Increase the strength of binding to the antigen
e. Improve bioavailability from the injection site

b. Reduce undesirable immune response against the antibody

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When reconstituting some protein drugs such as Neupogen, which of the following is sometimes
added at high concentration to block surface binding of the drugs to the plastic surface?
a. Dextrose
b. Human albumin
c. Sodium chloride
d. Lactose
e. Tween

b. Human albumin

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Which of the following is true regarding Lantus insulin?
a. It is a cloudy suspension at pH 4 because the insulin forms microcystals with zinc
b. It is a clear solution at pH 4 because its arginine units are uncharged
c. It is a cloudy suspension at pH 7.4 because it forms fine microcystals with zinc
d. It is a clear solution at pH 7.4 because its arginine units are charged
e. None of the above is true

c. It is a cloudy suspension at pH 7.4 because it forms fine microcystals with zinc

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In the table showing the top selling biotech products, which of the following is NOT one of their
therapeutic application?
a. Anticancer
b. Immunosuppression
c. Vaccine
d. Suppression of organ transplant rejection
e. Pain killing

e. Pain killing

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In the COVID-19 vaccines, ionizable phospholipids are one of the main ingredients. What is
their main role?
a. Form complexes with mRNA to entrap them in the nanoparticles
b. They provide “stealth” function
c. They stabilize the lipid structure of the nanoparticles
d. They serve as antioxidant
e. They are surfactants to avoid aggregation

a. Form complexes with mRNA to entrap them in the nanoparticles

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If you receive a newly marketed product named Gozillakingkongmab and are not sure about its storage/handling procedures, based on general knowledge about biotech drugs, which of the following should be avoided? Choose the BEST answer. a. Vigorous shaking b. Freezing c. Refrigeration at 4 o C d. A and B should both be avoided e. A, B and C should all be avoided

d. A and B should both be avoided

Avadar is a high molecular weight glycoprotein (MW = 123 kDa) with some hydrophobic amino acids, a few anionic, acidic amino acid units and multiple disulphide bridges. What is the most likely response of Avadar when it is diluted in a vehicle with low pH (e.g. pH 4)? a. will become more soluble as acidic amino acid units will become charged at low pH b. will become less soluble as acidic amino acid units will lose their charges at low pH c. will become more soluble as the disulphide links will become charged at low pH d. will become less soluble as the disulphide links will lose their charges at low pH e. will remain soluble regardless of pH change because at this molecular weight, the protein should be water-soluble

b. will become less soluble as acidic amino acid units will lose their charges at low pH

what is nanomedicine?

small devices with 100-300 nm in diameter to treat a disease or serve as a vehicle to carry therapeutic agents for disease treatment (also for diagnosis)

types of nanomedicine

-nanoparticles/nanospheres - liposomes - drug nanocrystals -micelles -quantum dots

particles made of solid lipids, polymers, or colloids, used for drug delivery (e.g. lipid nanoparticles, polymer nanoparticles, albumin nanoparticles)

nanoparticles or nanospheres

spherical vesicles made of phospholipids

liposomes

crystalline particle w/ dimension less than 1000 nm and useful for drug delivery when the drug is insoluble in water

nanocrystals

clusters of amphiphilic molecules for delivery of hydrophobic drugs

micelles

10-50 nm semiconductor (e.g. cadmium selenide), more often used for imaging, also proposed for cancer therapy

quantum dots

what type of nanomedicine includes emulsions or microemulsions

quantum dots

nanodelivery refers to

very small vehicles to deliver hard to deliver drugs (BCS class II to IV drugs)

why nanomedicine?

- solubilization of poorly soluble drugs - prevent degradation of unstable drugs - favorable PK (e.g longer 1/2 life, higher AUC>> improved bioavailability) -alters tissue distribution (e.g. BBB, can be penetrated by well designed nanosystems) - unique inrxn at cellular and intracellular levels -targeted delivery

BCS __: immediate dissolution and absorption "plenty of both" optimal

class 1

BCS __: dissolution limited "limited aqueous solubility"

class 2

BCS __: permeation limited "too water soluble or not enough permeability"

class 3

BCS __: bioavailability is unpredictable " not enough solubility or permeability"

class 4

what type of surface area distribute well on cell membrane (e.g. quantum dots for cell imaging)

large

endocytosis of nanosystems may sneak large therapeutic biomolecules across cell membrane (e.g. gene therapy, therapeutic peptides)

drug trafficking

challenges of nanomedicine

- PK is altered. behaviours of biomaterials also change at nanoscale. patient response can be unpredictable -antibodies, interferon,etc may also be elicited when being exposed to some polymers, proteins or synthetic lipids - immune system will remove foreign particulate matters through phagocytosis - extreme large surface area of nanosystems implies vulnerability to flocculation, coalescence - GMP issue ( control of size , charge, composition, sterility) -reproducability - upscalability -regulatory issues

how are nanocrystals manufactured

- downsizing bigger drug crystals (e.g. homogenization,milling) - micro-precipitation from drug solution

how are nanocrystals stabilized

w/ surfactants or amphiphilic polymer coating

consequence of nanocrystals not being stabilized

aggregation and creaming

when nanocrystals are sold in form of suspensions they are called ___

nanosuspensions

phospholipid molecules are ___. each has a hydrophilic polar head and hydrophobic tails

amphiphilic

__ have both lipophilic and hydrophilic compartments, so they can carry and deliver both lipophilic and hydrophilic drugs, as well as biomolecules (protein, DNA, RNA)

liposomes

True or False: liposomes are micelles

false ( they are NOT micelles)

A nanomedicine with a single bilayer lipid structure and has size of around 100 nm is likely _____________________

unilamellar

A nanomedicine with a multiple bilayer lipid structure and has size of 100- 1000 nm is likely _____________________

multilamellar

Which of the following may involve hours of milling of poorly soluble drug for preparation and their products generally need stabilizers or surfactants to avoid aggregation?

nanocrystals

what are the advantages of nanomedicine? a. protect the loaded drug from enzymatic degradation b.improve bioavailability of some drugs c. good at improving delivery of BCS class I drug d. help solubilize oily, poorly soluble drugs e. allow targeting of certain inaccessible organs

a. protect the loaded drug from enzymatic degradation b.improve bioavailability of some drugs d. help solubilize oily, poorly soluble drugs e. allow targeting of certain inaccessible organs

what drug is this? - brand name: rapamune -used for preventing organ rejection - 1st marketed nanocrystal drug product (2000) - prepared using "pearl mill" technique for downsizing

sirolimus

what drug is this? - brand name: Tricor - used for lowering triglyceride - practically insoluble - original crystalline formulation requires food for optimal oral absorption and bioavailability Nanocrystallized of Tricor - oral bioavailability increases independent of fed or fasted state - higher adhesiveness to the gut wall - making dosing regimen simplified

fenofibrate

__ is used for treatment of invasive infections. - large molecule; toxic

Amp-B

what formulation of Amp-B is this? - severe toxicity: nephrotoxicity, non-specific delivery, infusion-related toxicity -poor BBB penetration -dose limited

free Amp-B (e.g. Funizone)

t/f: in immunocompromised patients, free Amp-B often ineffective

true

what formulation of Amp-B is this? - bind Amp-B to cholesteryl sulfate - some reduction in nephrotoxicity

lipid complexed Amp-B (e.g. Amphotec)

what formulation of Amp-B is this? - improved solubility - reduced non specific binding - reduces toxicity - improves PK ( long circulation time) - higher doses allowed - better brain tissue permeation

liposomal Amp-B (AmBisome)

cheaper and more stable liposomal Amp-B is ...

fungisome

Which of the following ingredients in a liposomal formulation helps increase drug binding?

distearolyphophatidyl-glycerol

Which of the following ingredients in a liposomal formulation is an oil soluble antioxidant that chemically protect liposomes?

a- tocopherol

Which of the following ingredients in a liposomal formulation helps with the liposome bilayer structure?

hydrogenated soy phosphatidylcholine

doxil/ caelyx are called ___ liposomes

stealth

why are stealth liposomes called that? where does stealth come from?

mPEG coating

what drug is this? - commonly used for cancer chemotherapy - accumulative toxicity ( lethal CHF) - bind everywhere in body (large volume distribution and short half life)

doxorubicin

doxorubicin liposomes

- lipids conjugated with mPEG (avoids removal by immune system) - stay in circulation (small volume distribution and increased circulation - significant reduction in cardiotoxicity - enhanced accumulation in tumor sites

what drug is this? - paciltaxel bound to human albumin - avoid solvent in formulation - reduced toxicity (e.g. weight loss, neutropenia) - better efficacy for breast cancer and lung cancer - come as lyophilized "cake" of dry powder

Abraxane

the reconstituted suspension of Abraxane have to be ...

milky and homogenous without visible particulates

t/f: discard the Abraxane if foaming or clumping occurs

false ( wait until it subsides)

t/f: inject sodium chloride or diluent in a small manner to the wall of the vial and not directly to the drug to ensure wetting

true

active chemical entities of protein, peptide, or nucleic acid structure which exhibits an immunologic or pharmacodynamic effect. also known as molecular therapeutics, large molecule drugs, macromolecules, biologics

biotechnology drugs

a polymer of a.a. linked by peptide bonds

peptide dipeptide (2aa) tripeptide (3aa) oligopeptide (20-50 aa)

consists of one or more relatively long peptide. it has more than 50 aa units and typically has a 3D structure and S-S disulfide linkages

protein

a protein with sugar unit attached, typically on cell surface (e.g. monoclonal antibodies)

glycoprotein

proteins or peptides produced from the cells (bacteria, yeast or mammalian cells) transfected with recombinant DNA

rDNA

glucagon (29aa) calcitonin (32aa) glucagon like peptides GnRH/ LHRH VIP secretin are examples of ...drugs

peptide

insulin human growth hormone (HGH) are examples of ... drugs

protein

erythropoietin human chorionic gonadotropin antibodies are examples of ... drugs

glycoprotein

__ drugs - gene therapy - DNA vaccine - still at the experimental stage

DNA

__ drugs - mRNA vaccine - RNAi drugs (small interfering RNA/ si RNA and microRNA/miRNA) - antisense RNA - only mRNA has gone clinical

RNA

t/f: bioequivalent generic products are harder to develop. - fewer generic competitors even after patent expiry ( which means it is expensive)

true

t/f: epogen and neulasta needs to be protected from light

true

t/f: most biotech drugs require administration by injection

true

increasing absorption rate of injection

IV>SC>IM

why mRNA can't cross the cell membrane?

- large MW - highly negative charged - hydrophilic - easily degraded by high temp, by enzymes that break down RNA

mRNA is a BCS class __ drug

III (permeation limited)

pfizer and moderna vaccines use ionizable lipids to bind the negatively charged mRNA. what does ionizable mean?

becomes cationic at pH=4

design of mRNA is similar to liposomes except it does NOT have a __it is just a solid core and are often called lipid nanoparticles (LNP)

bilayer

mRNA as API:

nucleoside modified mRNA encoding the viral spike glycoprotein of SARS-CoV-2

PEG lipid is for

staying in circulation

DSPC as

phospholipid for structure

cholesterol

stabilize the structure of lipids

true or false: this would be soluble - smaller MW - peptide less than 5 aa - high charge - low hydrophobicity

true

t/f: most rDNA products have high MW. to keep them dissolved in aqueous environment, they tend to bear hydrophilic groups and preferably some charges

true

cationic aa (think of CAT in LA from sam and cat)

arginine and lysine (LA)

anionic aa

glutamate and aspartate

OH group: hydrophobic or hydrophilic

hydrophilic

phenylalanine has an aromatic group. hydrophilic or hydrophobic

hydrophobic

FC region (handle of fork)

interacts with the immune cells and does not look foreign to the immune system

FV region ( spikes of fork)

specificity/ targets and bind to receptors

immunoglobulin

protein sequence capable of eliciting a targeted immune response to a antigen - 2 heavy chains + 2 light chains

IgA, IgE,IgM,IgD,IgG,

immunoglobulin

any substance capable of promoting an immune response via immunoglobulins (e.g. bacteria cell walls, toxins, immunoglobulins and proteins)

antigen

an immunoglobulin capable of binding to the antibody and facilitating an immune response

antibody

several B-lymphocytes may respond to the same antigen, each produces antibodies with slight difference (recoginize and bind to differenct epitopes

polyclonal antibodies

antibodies come from the same cloned B-lymphocyte - same protein structure - highly specific to a particular antigen - elicits a specific immune response

monoclonal antibodies

__ is a humanized monocolonal antibody. blocks a certain receptor that prevents immune system to attack the implicated cells. used for cancer immunotherapy (e.g. head and neck, melanoma,lung and cervical)

keytruda (pembrolizumab)

__ is the first whole human monoclonal antibody drug that blocks TNFa that triggers immune responses. it is used for autoimmune disorders (e.g. RA, crohn's disease, ulcerative colitis, psoriasis)

humira (adalimuman)

ozempic (semaglutide) is a __ approved for treatment of type II diabetes. adminstration is SC (as ozempic) by PO (as rebelsus) approved for weight loss * as SC injection (wegovy)

glucagon like peptide

Nano and biotech drugs Flashcards

(112 cards)