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SR PM4B > Advanced Drug Delivery 6 - Microparticles and Nanoparticles > Flashcards

Advanced Drug Delivery 6 - Microparticles and Nanoparticles Flashcards

1
Q

What are Microparticles

A

Particles in the micro size range, normally between 3-800 µm
Two types: microcapsules, microspheres

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2
Q

What is a microsphere

A

No distinct region
Matrix system

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3
Q

What is a microcapsules

A

Two distinct regions: external wall and central core
A reservoir system since they consist of two parts

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4
Q
A

Microcapsule: has distinct regions
Technically a polynuclear microcapsule because it has multiple nuclei

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5
Q

Which one is which: microcapsule, microsphere

A

Top: microcapsule - distinct regions (external wall, central core), reservoir system
Bottom: microsphere - no distinct region, matrix system

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6
Q

Administration routes of Microparticles

A

IV, directly to specific compartment (e.g. inhalation, local injection, SC)

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7
Q

What does body distribution of Microparticles depend on

A

size, shape, surface charge, surface tension

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8
Q

5 requirements of materials used to make Microparticles

A

chemically inert
non-toxic (not the drug so will not accept any toxicity!)
biocompatible
biodegradable if necessary
easy to sterilise - esp for injections

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9
Q

Examples of materials used to make Microparticles

A

Proteins (e.g. albumin, gelatin)
Polysaccharides (e.g. starch, cellulose, chitosan)
Polyesters (PLA, PGA, PLGA)
Polyanhydrides
Polyvinyl derivatives
Polyacrylates
Others e.g. waxes

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10
Q

5 applications of Microparticles

A

MR
Conversion of liquids into pseudo solids
Protection from external environment
Mask flavour and odour - organoleptic properties
Reduce gastric irritation

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11
Q

How to convert liquids into pseudo solids using Microparticles

A

Encapsulate the liquid API to form a microcapsule, this makes it become a pseudo solid

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12
Q

3 Steps to prepare Microparticles

A
  1. Disperse drug in the polymer (constituent) solution
  2. Coacervation (or phase separation) - using a trigger that makes polymer precipitate so you can form Microparticles
  3. Hardening of coating
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13
Q

4 examples of coacervation

A

Changing temperature of polymer solution
Salting out
Adding non solvent
Inducing a polymer-polymer interacition

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14
Q

Ways to harden coating

A

Promote cross linking or cool the system down

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15
Q

Coacervation: changing temperature of polymer solution

A

Materials have different solubilities at different temperatures
There is a dispersion of the drug in the polymer solution - polymer is dissolved
Change to a temperature at which polymer is no longer soluble so that it precipitates out and you form Microparticles

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16
Q

Coacervation: salting out

A

Drug is disperse in a solution of a polymer
Add an inorganic salt (contains anions + cations)
Water molecules will preferentially interact with the charged ions
Polymer will precipitate out, Microparticles will form

17
Q

Coacervation: adding a non solvent

A

Polymer is solubilised in solvent A
Add solvent B which is miscible (can be mixed) in solvent A
Solvent B needs to be a poor solvent for the polymer (polymer is insoluble in this)
Polymer will precipitate out
Microparticles will form

18
Q

Coacervation: inducing polymer-polymer interaction

A

Add a second polymer to the solution that interacts with the first polymer and makes it precipitate out
Formation of Microparticles

19
Q

Preparation of Microparticles via interfacial polymerisation

A

Start with a monomer and make the polymerisation in situ
Polymer is formed at the interface between two immiscible liquids: organic phase and aqueous phase + dissolved drug
By addition, you can obtain microspheres
By Condensation, you can form microCapsules

20
Q

Preparation of microspheres by heat or chemical denaturation

A

Good way to make Microparticles when material is protein
Oil phase, add an aqueous solution of protein + drug
Mix the two to form emulsion: water in oil
Need a trigger to denature protein so that Microparticles can form
Chemical: add glutharaldehyde or butadiene which cross slinks protein and it will precipitate out
Physical: heat system 100-170C to denature and precipitate protein out

21
Q

Spray drying to form Microparticles

A
  1. atomisation of liquid feed ( also containing drug ) into fine droplets
  2. mix spray droplets with heated gas system, allowing liquid to evaporate and leave a dried solid
  3. dried powder separated from gas stream and collected
22
Q

5 advantages of spray drying to form Microparticles

A

quick and reproducible
control of particle size
low cost
good yield
applicable to heat sensitive materials

23
Q

limitations of spray drying to form Microparticles

A

need polymers that give low viscosity solutions
need small droplets
water soluble compounds have poor encapsulation

24
Q

5 ways that drug is released from microspheres

A

Erosion
Disintegration of microsphere in body to release API
Swelling of microsphere, and API diffuses out
Desportion and diffusion
Ionic exchange

25
Q

Drug release from microspheres: desorption & diffusion

A

In the microsphere, some of the drug could be inside and some could be adsorbed on surface via interactions
Once administered, there is a change in environment
Adsorbed drug may come off and diffuse into the body fluids

26
Q

Drug release from microspheres: ionic exchange

A

Adsorbed drug is an ion - a charged drug
Administer microsphere
Many ions present tin body that can interact and swap with the drug

27
Q

What are nanoparticles

A

Particles in the nano size range: nm
Two types: nano capsules and nanospheres

28
Q

Nanocapsules

A

2 distinct regions so are a reservoir system
External wall and central core

29
Q

Nanospheres

A

Matrix system as they only have a single region

30
Q

Location of API in nanoparticles

A

API can be dissolved, physically entrapped or adsorbed on the surface
No covalent bonds - just interactions

31
Q

3 ways to make nanoparticles

A
  • Some scientists make PDG and from them they make nanoparticles (hybrid system)
  • Using ready made polymers
  • Methods that require polymerisation
32
Q

2 polymers most commonly used for nanoparticles

A

PLA and PLGA

33
Q

Preparation of nanoparticles using solvent evaporation

A

Two beakers: polymer + drug and water +emulsifying agent
Mix the two to form an oil water emulsion
Droplets of solvent contain the polymer + drug
Solvent evaporation to form nanoparticles
Nanoparticles will precipitate and can be collected

34
Q

Toxicity of Microparticles and nanoparticles

A

Generally acute toxicity is low as it depends on materials used and they are no toxic
Toxicity depend son size and number of particles injected
Longer term toxicity:
- consider possibility of material starting to accumulate in body
- need to ensure material is being eliminated form body e.g. by degradation and bioerosion

35
Q

Biodegradation as a method to eliminate Microparticles and nanoparticles from body

A

Polymer gets broken down at level of monomer as bonds between monomers are biodegradable
e.g. PLGA: ester bonds break down

36
Q

Bioerosion as a method to eliminate Microparticles and nanoparticles form body

A

Points of junctions in polymer get broken down
Don’t end up with individual monomers, but smaller components of the polymer
These are small enough for body to degrade them

37
Q

Problems with IV injections of nanoparticles and a solution

A

Nanoparticles can be endocytosed by macrophages of the reticular endoplasmic system (RES)
This is good if we are targeting the liver or spleen
This is bad if it reaches other tissues because it won’t be effective
Strategy: PEG-coated nanoparticles to mask them from macrophages

38
Q

What is ABRAXANE

A

Nanoparticle on the market
contains palictaxel
used in cancer therapy for advanced metastatic breast, pancreatic and NSCLC

SR PM4B (41 decks)

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