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Encapsulation technology: Principles and Applications

In Woo Cheong, Ph.D. Associate Professor

Department of

Applied Chemistry, Kyungpook National University

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Backgrounds

Small is not only beautiful but also eminently useful - Prof. JH Fendler

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What are capsules ? Nano- or micron-sized containers !!

Core materials: liquid, solid, gas, protein, cell, etc Shell materials: (i) Organics: polymers, lipids, surfactant (gelatin, urea-urethane, melamine resin, block copolymer, etc) (ii) Inorganic ceramics (SiO2, TiO2, Al2O3, etc) (iii) O/I hybrids (R-SiO2, R-TiO2, R-Al2O3, etc)

From “Smart Capsules for Flexible Electronics” by Dr. S.S. Lee at KIST

oil

In-situ polymerization

oil

Interfacial polymerization

oil

Complex coacervation

Emulsion-based encapsulation (o/w system)

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Why do we know about capsules ?

As reaction container

Protection of vulnerable stuff

Mass transport (release)

Nanoparticle formation Polymerization Coupling rxn, etc. Field responsive materials

Bio-active materials Cell & protein encapsulation Fragrant oils, etc.

Drug delivery Anti-corrosive coating Self-healing Redox rxn, etc.

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Back to the principle, ”How to make capsules ?”

Thermodynamic Consideration

Torza S, Mason SG, J Colloid Interface Sci., 33, 6783 (1970)

Spreading Coefficient

Si = γjk - (γij + γik) where, γjk is interfacial tension between j and k phases. Condition for complete engulfing of phase 1 by phase 3 S1 < 0(γ23 < γ12), when S2<0 and S3>0

1: hydrophobic liquid, 2: water, 3: polymer

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Basic Understanding: - Surface Phenomena

Why most of the capsules are spherical ?

The molecules at the surface must have a higher energy than those in bulk, since they are partially freed from bonding with neighboring molecules !

Water

Air

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Basic Understanding: - Surface Phenomena

Therefore, work must be done to take fully interacting molecules from the bulk of the liquid to create any new surface surface tension

How to measure the surface tension ?

Then how about with solid materials ?

A Work

Wc

Wc = 2ⅹsurface energy (2ⅹAⅹγs)

Unfortunately, we can’t define the surface area exactly…

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Basic Understanding: - Surface Phenomena

Measuring contact angle !

θ

γLV

γLS

γSV

θ

liquid

vapor

dl*

dl solid

Top-view

ldlldlldldG SVLVSL γγγ −+= *

θcos* dldl =

θγγγ cosLVSLSV +=Therefore, …Young equation

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Basic Understanding: - Surface Phenomena

Then how to determine γSL and γSV ?

• Measure the contact angle of liquids with various surface energy (γLV) and plot γLV vs. cosθ.

•Extrapolate it with the value of θ becomes 0 (we call this value γc, complete wetting) and then we can obtain (γc =) γSV.

• For specific liquid system, we apply γSV value and get γSL.

20 30 40 50 γLV/mJm-2

cosθ

1.0

γc

γc = γSV

(complete wetting, γSL0)

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Basic Understanding: - Surface Phenomena

• Surface energy of solids is closely related to its cohesive energy (The higher the surface energy, the higher its cohesion)

• Surrounding (water, vacuum, air, etc.) property significantly affect the force required to make a new surface (i.e., crack propagation)

• At the equilibrium, θγγγ cosLVSLSV +=

If we add surfactant, drop will spread, γSV - γSL - γLV > 0

Here we can define a parameter (Spreading coefficient); SLS = γSV - γSL - γLV

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How to make capsules ? Thermodynamic Consideration

Torza S, Mason SG, J Colloid Interface Sci., 33, 6783 (1970)

Spreading Coefficient

Si = γjk - (γij + γik) where, γjk is interfacial tension between j and k phases. Condition for complete engulfing of phase 1 by phase 3 S1 < 0(γ23 < γ12), when S2<0 and S3>0

1: hydrophobic liquid, 2: water, 3: polymer

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Basic Understanding: - Colloidal Phenomena

Grind to submicron size

bulk colloid “true” solution

Fundamental forces operate on fine particles 1. A gravitational force (settling or creaming depends on density difference) 2. Viscous drag force (resistance to motion) 3. Natural kinetic energy of particles and molecules (Brownian motion)

What are Colloids ?

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Basic Understanding: - Colloidal Phenomena

분자Colloid 입자Colloid Micelle Colloid

Egg, Protein, PVA, etc.

Natural rubber, Latex paint, milk, ice-cream, etc.

Detergent, Shampoo, Liposome, etc.

Type of Colloids

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Basic Understanding: - Colloidal Phenomena

Large surface area :Adsorption property

Light scattering : Tyndall phenomena

Electrically charged : Elecrophoresis Etc.: Brownian motion

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Basic Understanding: - Colloidal Phenomena

• Colloidal particles prepared from natural or synthetic process in nano and micron-sizes.

• Large surface area • Various typical properties (surface property) • Mineral, metals, protein, polymer, etc.

SEM image of heterocoagulated polymer particles

starch latex paint waste water milk treatment

Natural Rubber latex

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Thermodynamic aspect Phase transition accompanies change in standard free energy, ∆Gf = γ ∆A

> 0 < 0

Colloidal stability is poor (Lyophobic) Coagulation Thermodynamically stable (Lyophilic)

∆Gf

∆Gf

∆Gf Bulk Colloids

Basic Understanding: - Colloidal Phenomena

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Thermodynamic aspect Lyophobic colloids, even if they are thermodynamically unstable, can be made “metastable” for long periods of time if an energy barrier of sufficient height can be erected between the bulk and colloidal state. “Kinetically stable”

Hydrophobic tail

Hydrophilic head

Basic Understanding: - Colloidal Phenomena

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Synthesis

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Historical stuffs • Christopher Columbus discovered

natural latex.

• 1839-1844 Charles Goodyear – Vulcanized latex was invented.

• Before World War I, synthetic rubbers from emulsion (exactly not from emulsion, but from suspension).

• 1920s - World War II, “true” emulsion polymerization was conducted.

Natural rubber tree: Hevea Brasilensis

30-40% 100% cis-Polyisoprene 50-60% Serum Etc. Lipids, Proteins, Inorganics

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Historical stuffs Original reasoning: they assumed they could polymerize emulsion droplets ⇒ polymer latex:

free-radical initiator

Poor quality products because of wrong mechanism

water Monomer droplet

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Historical stuffs

Polymer particles ~ 100 nm diameter each containing many polymer chains, stabilized by surfactant

water

monomer

surfactant solution initiator solution

latex (polymer particles 100 nm diameter)

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Heterogeneous Polymerization Generation of tiny particles

From the precept of laborious works on kinetics: Micelles or monomer droplet can be a primary locus of reaction … a state we call “nano- or micro-reactor”

Droplets

∆E

Nano-reactor

Small size Protection Mass and heat transfer

1018~1021 nano-compartments/L

RXN

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Heterogeneous Polymerization Why nanoparticle ?

– Better storage stability

– Better transparency

– Fast film formation rate and permeability

– High reaction rate

Energy of Particle (Etot) = Ei + Es = eiV + γA ei: Energy per unit volume γ: Surface Energy per unit volume Therefore, Etot/unit volume = ei + γ(A/V) Dp (nm) A/V(cm-1) 1 6x107

10 6x106 100 6x105

A Problem: Aggregation or flocculation of nanoparticles

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Heterogeneous Polymerization

Type Typical Particle Radius

Droplet size Initiator Continuous

Phase Discrete phase

(particles)

Emulsion 50 – 300 nm ≈ 1 – 10 µm water or oil soluble Water

Initially absent, monomer-

swollen polymer particles form

Dispersion ≥ 1µm - oil soluble

Organic (poor solvent

for formed polymer)

Initially absent, monomer-

swollen polymer particles form

Suspension ≥ 1 µm ≈ 1 – 10 µm oil soluble Water

Monomer + formes polymer in pre-existing

droplets

Inverse Emulsion 102 – 103 nm ≈ 1 – 10 µm

water or oil soluble

oil Monomer,

cosurfactant + formed polymer

Microemulsion 10 – 30 nm ≈ 10 nm water soluble Water

Monomer cosurfactant +

Formed polymer

Miniemulsion 30 – 100 nm ≈ 30 nm water soluble Water

Monomer, cosurfactant +

formed polymer

The differential types of heterogeneous polymerization systems

www.andrew.cmu.edu/user/kemin/Research.htm

Suspension Emulsion Miniemulsion Microemulsion

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Emulsion Polymerization Free-radical polymerization

• Usually vinylic: CH2= CR1R2 • R1 = H:

– R2 Name – –Ph styrene – –CH=CH2 butadiene – –Cl vinyl chloride – –CO2H acrylic acid – –CO2Me methyl acrylate (butyl, …) – –OCOCH3 vinyl acetate

• R1 = CH3:

– –CO2Me methyl methacrylate (MMA) (butyl, …) • R1 = Cl:

– –CH=CH2 chlorobutadiene (neoprene)

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Emulsion Polymerization • Initiation:

– e.g. R–N=N–R → 2R• + N2 ; rate coefficient kd R • + M → RM •

• Propagation: (monomer unit M) – –Mn• + M → –Mn+1• rate coefficient kp

• Termination:

– 2R• → dead polymer rate coefficient kt

• Transfer, e.g. to monomer: – –Mn• + M → –Mn + M • rate coefficient ktr – M • then starts another chain

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Emulsion Polymerization

Core/shell Hemisphere Occlusions

Various morphologies: electron microscopic images

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Emulsion Polymerization Various morphologies: electron microscopic images

S Omi et al., J Applied Polym Sci., 66, 7, 1327 (1998)

Snowman-like Porous morphology

Rugby ball-like Raspberry-like

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Emulsion Polymerization

Transmission Electron Micrograph Showing the Cross-Sections of OsO4-Stained Two-Stage (20 PS/80 (S/B)) Latex Particles

100 nm

Polystyrene Core (20 parts)

S/B Copolymer Shell (80 Parts)

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Emulsion Polymerization TEM sample preparation techniques

Shadowing

Pt, Cr particles [RuO4 제조의 예] 2NaIO4 + RuO2 RuO4 + 2NaIO4

Staining

Microtoming

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Microemulsion Polymerization • Microemulsion: transparent liquid system consists of at least

ternary mixtures of oil, water, surfactant. • It exhibits continuous or bicontinuous structure with < 100 nm

scale.

www.baschem.co.uk

W/O

O/W

Oil (O)

Water (W) Surfactant (S)

Bicontinuous

Liquid crystalline

W

O

O

W I

W II

W III

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Microemulsion Polymerization • Surfactants

– SDS : needs co-surfactants, short chain alcohols – Nonionics, some cationics (e.g., CTAB, DTAB), double chain

surfactants (e.g., Aerosol OT) need no co-surfactants

• Features – Thermodynamically stable – Enormous inner surface area – Various morphologies – No steady state reaction rate – Inorganic particle formation – Large amount of surfactant (7-15wt%)

Andrey J. Zarur and Jackie Y. Ying Nature 403, 65-67

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Microemulsion Polymerization Surfactant system: wet template

os lavN /=Packing parameter (shape factor)

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Microemulsion Polymerization

Hsiang Y. W. et al, Chem Mat 2005, 17, 6447

Zhaoping Liu, et al, Langmuir 2004, 20, 214

K. Landfester et al., Macromolecules 2000, 33, 2370

JS Jang et. al., Chem Comm, 2003

Making various morphologies

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Emulsification Techniques • Features

– Post emulsion process – Uncontrollable particle size distribution – Methods:

• Direct emulsification – External surfactant assisted emulsification – Neutralization emulsification

• Other emulsification methods – Emulsification-diffusion emulsification – Nanoprecipitation – Dialysis – Membrane emulsification – Self-assembly technique

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Emulsification Techniques Emulsification-diffusion emulsification

Water + Stabilizer

Emulsification

Adding excess water

Solvent diffusion

PLGA + Solvent

50 nm50 nm50 nm

TEM micrograph of PLGA nanoparticles produced by ED method.

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Emulsification Techniques Nanoprecipitation and dialysis methods

Nanoprecipitation Dialysis

water

emulsifier

polymer solvent drugs

microsyringe pump piezoelectric nozzle

dialysis tube PLGA

hydrophobic probe

TEM micrograph of core-type particles produced by nanoprecipitation.

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Emulsification Techniques Membrane emulsification

Optical micrograph of W/O/W multiple emulsion droplet containing vitamin C by membrane emulsification. O/W W/O/W

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Emulsification Techniques

worms vesicles Starfish vesicle

lamellae large compound vesicles (LCV)

Self-assembly technique by Block Copolymers

Micellization of PS-PAA block copolymers under different conditions (i.e., ionic strength, concentration of polymer, MDF/water ratio, etc.)

Amphiphilic block copolymer

Micelles

vs. Gels

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Block Copolymers A living free-radical polymerization

– No termination or chain transfer – Radical chain remains active when all the monomer is used up – Propagation continues when additional monomer is added

– Block copolymer formation! – Example : atom transfer radical polymerization

. . CH3CHCl + Cu(I)(bpy) CH3CH + Cu(II)(bpy)Cl

φ φ .

Initiation

CH3CH + CH2=CH CH3CHCH2CH φ φ φ Propagation

. Atom transfer CH3CHCH2CH + Cu(II)(bpy)Cl CH3CHCH2CHCl + Cu(I)(bpy)

φ φ φ φ

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Block Copolymers Formation of block copolymers

(a) sequential “controlled/ living “block copolymerization

(sequential addition of monomers)

(b) coupling of linear chains

containing antagonist functions ( X and Y )

(c) switching from one

polymerization method to another

(d) use of a dual (“double-

head”) initiator consisting of two distinct initiating fragment ( I1 and I2 )

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Block Copolymers Crosslinking

Shell crosslinking J Am Chem Soc 2000;122:3642–51.

Core crosslinking Macromolecules 2000;33: 4780–90.

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Block Copolymers Stimuli-responsive nano-assemblies

– Intelligent, smart, environmentally sensitive, etc. – Stimuli : light, temp., solvent, pH, chemicals, etc. – Drug release, encapsulation, intelligent switches

PS-co-P2VP-co-PEO

Core/shell/corona

2-(dimethylamino)-ethyl methacrylate 2-(diethylamino) ethyl methacrylate Poly(DMAEMA/DEAEMA) diblock copolymer

Chem Commun 1997;671–2.

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Applications

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Applications

• Anti-corrosive coatings – Sacrificial means: zinc-rich

coating

– Barrier effect: polymer coatings, inorganic filler (eg. MMT): increases pathway by parallel arrangement, stainless flakes, glass flakes, etc.

– Inhibition: Cr and Pb-based pigments metal phosphate, silicate, titanate or molybdate compounds

• Self-cleaning coatings – Hydrophobic-hydrophilic

effects – Lotus effect – Photo-reactive : TiO2

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Applications Self-cleaning coating with TiO2

– Photo-catalytic titanium dioxide (TiO2): A strong oxidation power & super-hydrophilicity

– TiO2 coating cannot be coated directly onto an organic paint surface as this will attack the paint surface, causing a phenomenon so called paint-chalking.

Substrate

: inorganic linker : organic or polymer

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Applications

52 days 32 days 24 days

Copper plating coating Composite coating 2 days

8 days 12 days 16 days

Swapan K G, Functional Coatings, Wiley-VCH, 2006.

Encapsulation of Ultra-hydrophobes

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Applications

S. R. White et al, Nature 2001, 409, 794

Self-healing Plastics Matrix: Epoxy Microcapsule : Urea-formaldehyde + dicyclopentadiene (DCPD) Catalyst:

U of Illinois at UC

coating without capsule

coating with capsule

0 hr

24 hrs

48 hrs

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Applications pH-induced Micellization

Angew. Chem. Int., Ed 2003;42:1516–9.

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Applications E-paper

Characteristics : • Flexible like news paper • Wide-angular readability • Low energy (No back-light) • Potable (light-weight)

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Applications

+/- charged core-shell particle

~ 200 nm

20 - 50 µm Nature, 394, 16, July 1998.

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Applications

prepolymer migration and crosslinking

in situ polymerization

Urethane prepolymer chain extender

interfacial polymerization

transparency durability flexibility impermeability thermal and chemical resistance

Characteristics of shell materials

E-paper 100μm

From “Smart Capsules for Flexible Electronics” by Dr. S.S. Lee at KIST

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Previous and Current Works on Encapsulation

MF@Fragrant oil J. Microencapsulation, 19(5), 559 (2002)

PAni@PS Synthetic Metals, 151(3), 246 (2005)

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Previous and Current Works on Encapsulation

Phase Change Materials

PCM

Bulk PCM

Microencapsulated PCM

Nanoencapsulated PCM

100 nm TEM image of PCM nanocapsule prepared by using ultramicrotome

Temperature ( ℃)

0 200 400 600 800

Wei

ght (

%)

-20

0

20

40

60

80

100

120 60% PCM PS CapsulePure OctadecanPolystyrene

TGA curve for capsulation efficiency analysis

Octadecane

Polystyrene

Octadecane@PS Korean Patent 10-0612139 (2005)

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Previous and Current Works on Encapsulation

Phase Change Materials

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Previous and Current Works on Encapsulation

Multi-walled Carbon Nanotubes

Macromol. Res., 14(5), 545 (2006) Korean Patent 2006-94071 Korean Patent (출원) 2008-0046401 (2008) Composites Sci. Tech., accepted in 2008

CNT

Amphiphilic Macromolecules

57 Kyungpook National University