4. Drug delivery

Question 1

Give examples of applications of nanotechnology in life sciences which use the iv delivery route.

Answer 1

• treatment of cancer, siRNA and gene delivery, intracellular infections.

Question 2

Give examples of applications of nanotechnology resulting in improved drug delivery via the oral route.

Answer 2

improvement of solubility, delivery of peptides, proteins and vaccin

Question 3

describe the evolution of drug delivery systems since the 1970s

Answer 3

sof natural organic drug carriers, soft synthetic drug carriers, hard inorganic particles for imaging and drug delivery

Question 4

Mention 5 forms in which can you deliver a drug using nanomaterials.

Answer 4

as a nanocrystal of the active substance or embeded in nanocarriers (depo, matrix, dendrimer, layer-by-layer)

Question 5

What are the possible benefits of using nanomaterials in drug delivery?

Answer 5

-tissue targetting (efficiency, toxicity), protection against degradation (clearance, dosing frequency), use of enhanced permeability and retention effect (EPR)

Question 6

Which pre-requisits must be fulfilled before a drug can be absorbed into the blood?

Answer 6

the active substance needs to have solubility and permeability

Question 7

What are the consequences when a drug is poorly soluble?

Answer 7

• poor and variable bioavailability, no dose-response, slow onset of action

Question 8

How are poorly soluble compounds being called?

Answer 8

brick dust, grease balls

Question 9

The Lipinski rule of 5 is used for the selection of candidate drugs for further development. Which type of drugs?

Answer 9

drugs to be given orally, absorbed via passive diffusion.

Question 10

Give the rules of Lipinski.

Answer 10

-

Question 11

What does the Ostwald-Freundlich equation describe?

Answer 11

• the relationshipe between solubility and particle size, in similarity to the Kelvin equation for the condensation of gasses. - smallest particles dissolve first

Question 12

Why is the solubility of irregular particles underestimated by Ostwald - Freundlich?

Answer 12

xx

Question 13

What is supersaturation and how can you prolong this?

Answer 13

• more dissolved than in equilibrium situation. rate nucleation and rate of crystal growth.

Question 14

Describe 5 models of nucleation and growth

Answer 14

LaMer burst nucleation, Ostwald and digestive ripening, coalescence and oriented attachment, finke-watzky 2 step mechanism, intraparticle growth

Question 15

What is nucleation?

Answer 15

• Wikipedia: Nucleation is typically defined to be the process that determines how long an observer has to wait before the new phase or self-organised structure appears.

Question 16

What are the benefits of using nanosusspensions, and challenges?

Answer 16

• higher bioavailbility, less variability due to food, increased rate of absoprtion, improved absorption of higher doses (tox testing), rapid formulation development ? - agglomeration

Question 17

Mention characteristics of an amorphous state

Answer 17

short-range order (?), low enthalpy of dissolution, metastable, recrystalise at varying T, rel humidity, p and agitation.

Question 18

How can you stabilise an amorphous compound using nanotechnology. Give an example.

Answer 18

• Pb in carbon nanotubes. amorphous compound in a poreous nanomaterial Study with CaCO3; amorpheous, vaterite (poreous), aragonite (non-poreous), calcite (non-poreous) ibuprofen in upsalite

Question 19

Cancer treatment. Why may NPs be a good tool for the passive targetting of tumor tissue?

Answer 19

• poor lymfatic draining, high vascularisation, leaky vessels. EPR effect

Question 20

What are the important physicochemical characteristics of rigid core nanoparticles to enable an optimal bioavailability?

Answer 20

• zeta-potential (neg); size (100-200 nm); hydrophylicity (high) ; these characteristics are good for Enhanced Permeability and Retention.

Question 21

How do you avoid RES (reticuloendothelial system = part of immune response)?

Answer 21

• polyethylene glycol of brush type (vs mushroon type (intermediate PEG density) and pancake type)

Question 22

Describe 2 examples of the use of nanothechnologically-induced hyperthemia.

Answer 22

• photothermal plasmon resonance (Au nanorods); magnetic hyperthermia through Néel or Brownian relaxation.

Question 23

You want to develop a treatment to eradicate a tumor by hyperthermia induced by Au nanorods. At which wavelength should the rods preferably absorb?

Answer 23

NIR (650 - 900 nm) because hemoglobin has minimal absorption below that and water above that.

Question 24

What are today’s challenges for the use of nanotechnology in cancer treatment?

Answer 24

• variable EPR effect, rapid clearance, drug resistance, inefficient cargo delivery (?)