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HANA- Part 4 pM4B 2 > 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
  1. Chemically inert
  2. Non-toxic
  3. Biocompatible
  4. Biodegradable if necessary
  5. 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
  1. MR
  2. Conversion of liquids into pseudo solids
  3. Protection from external environment
  4. Mask flavour and odour - organoleptic properties
  5. 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)
  3. Hardening of coating
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13
Q

Coacervation

A

The process by which a polymer solution separates into two phases

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14
Q

4 ways to induce coacervation

A
  1. Changing temperature of polymer solution
  2. Salting out
  3. Adding non-solvent
  4. Inducing a polymer-polymer interaction
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15
Q

Ways to harden coating

A

Promote cross linking or cool the system down

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16
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
17
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
18
Q

Coacervation: adding a non solvent

A
  • Polymer is solubilised in solvent A
  • Add non-solvent
  • Will cause polymer to become less soluble and associate with each other
  • Forms a dense liquid phase (coacervate) and a dilute liquid phase (supernatant)
  • Polymer will precipitate out
  • Microparticles will form
19
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
20
Q

Preparation of Microparticles via interfacial polymerisation

A
  1. Start with a monomer and make the polymerisation in situ
  2. Polymer is formed at the interface between two immiscible liquids: organic phase and aqueous phase + dissolved drug
  3. By addition, you can obtain microspheres
  4. By condensation, you can form microcapsules
21
Q

Preparation of microspheres by heat or chemical denaturation

A

Good way to make Microparticles when material is protein

  1. Oil phase, add an aqueous solution of protein + drug
  2. Mix the two to form emulsion: water in oil
  3. Need a trigger to denature protein so that Microparticles can form
  4. Chemical: add glutharaldehyde or butadiene which cross links protein and it will precipitate out
  5. Physical: heat system 100-170C to denature and precipitate protein out
22
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
23
Q

5 advantages of spray drying to form Microparticles

A
  1. quick and reproducible
  2. control of particle size
  3. low cost
  4. good yield
  5. applicable to heat sensitive materials
24
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
25
Q

5 ways that drug is released from microspheres

A
  1. Erosion
  2. Disintegration of microsphere in body to release API
  3. Swelling of microsphere, and API diffuses out
  4. Desorption and diffusion
  5. Ionic exchange
26
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
27
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
28
Q

What are nanoparticles

A

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

29
Q

Nanocapsules

A
  • 2 distinct regions so are a reservoir system
  • External wall and central core
30
Q

Nanospheres

A

Matrix system as they only have a single region

31
Q

Location of API in nanoparticles

A

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

32
Q

3 ways to make nanoparticles

A
  1. Some scientists make PDG and from them they make nanoparticles (hybrid system)
  2. Using ready made polymers
  3. Methods that require polymerisation
33
Q

2 polymers most commonly used for nanoparticles

A

PLA and PLGA

34
Q

Preparation of nanoparticles using solvent evaporation

A
  1. Two beakers: polymer + drug and water +emulsifying agent
  2. Mix the two to form an oil water emulsion
  3. Droplets of solvent contain the polymer + drug
  4. Solvent evaporation to form nanoparticles
  5. Nanoparticles will precipitate and can be collected
35
Q

Toxicity of Microparticles and nanoparticles

A
  • Generally acute toxicity is low as it depends on materials used and they are no toxic
  • Toxicity depends on 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 from body e.g. by biodegradation and bioerosion
36
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
37
Q

What is ABRAXANE

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

HANA- Part 4 pM4B 2 (35 decks)

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