1. Emulsion Polymerization
External variable (surfactant concentration) used to increase BOTH molecular weight as well as rate of polymerization
Colloidal system easy to control
Thermal, viscosity issues
Reaction mixture in form of final product for coatings
Reaction product needs to be isolated from aqueous latex for many applications like rubber, elastomers, PVC, fluoropolymers (C8 issue), etc

2. Variables and Other Characteristics
Redox Initiators
Hydrogen Peroxide w/ Ferrous Ion
Surfactant-Free Emulsion Polymerization
Initiator fragment affords amphiphilic character
Phase transfer catalysis (cyclodextran)
Microemulsion, Miniemulsion
Inverse emulsions
Core-Shell Particles
pH Control: Hollow Particles

3. Various Emulsions Emulsion Polymerization (macro)
Classic aqueous system
Particles range from nm
Microemulsion Polymerization
Optically clear, smaller particles
No droplets, just micelles
Miniemulsion Polymerization
Between macro and micro systems, monomer droplets smaller than in macro systems

4. Inverse Emulsion Polymerization
Standard emulsion polymerization uses water as the continuous phase, or oil-in-water (O/W)
Inverse emulsions use:
Oil as the continuous phase, or water-in-oil (W/O)
Hydrophilic monomer (or aqueous solution of monomer) dispersed in oil, i.e. xylene
Like acrylamide
Oil-soluble initiator
Surfactant

5. Surfactants
H2O
Oil

6. Surfactant Assemblies - Rich Morphologies
cationic
surfactant
anionic R V M
Vesicles
Rod-like Micelles
Micelles
Multi
V + L a
Multiphase Region
Vesicles and Lamellar Phase
5% SDBS
Water -
5% CTAT 1% 2% 3% 4%
V+L

7. Controlled Radical Polymerization in Microemulsion
Monomer-Swollen Micelles
Monomer Diffusion
Microemulsion Nanoparticles M M P•
PM•
Polymer Particle
Liu, S. Y.; Kaler, E. W. et al. Macromolecules 2006, 39, 4345

8. Design of Polymeric Nanogels for DNA Delivery
Research Objectives:
Design nanogels < 200 nm in diameter using inverse micro-emulsion techniques with excellent solution stability (w/o toxic solvents!)
Control release profile of DNA by selection of monomer and crosslinker
composition and concentration
3. Attach targeting ligands to surface of nanogels
We want to engineer nanogels with various release profiles. We are first concerned with the diffusion pathway. Diffusion can be slowed by the incorporation of cationic monomers or by increasing the crosslinker density.
It is important to start with the first biological barrier, and create a stable system which can be later tuned…
Eventually, we will have to attach targeting ligands to the surface, but we have not done this in our preliminary work.
Release of DNA
Diffusion Pathway
McAllister, K.; Sazani, P.; Adam, M.; Cho, M.; Rubinstein, M.; Samulski, R. J.; DeSimone*, J. M. J. Am. Chem. Soc. 2002,

9. Microemulsion Polymerization and Isolation of Nanogels
Addition of
Initiator to
oil phase and
free radical
polymerization
Removal of
heptane and
surfactant
by extraction
and dialysis
Step 1:
Form
microemulsion
Step 2:
Polymerize
microemulsion
Step 3:
Extract and
purify nanogels

10. Designing Polymeric Nanogels
Monomers
Nanogels
Increasing Crosslinker
Increasing Charge +
PEGdiacrylate n=8
2-Hydroxyethylacrylate
2-Acryloxytrimethyl-
ammonium chloride

11. Before Polymerization Crosslinker Concentration (wt %)
Dynamic Light Scattering of Microemulsions Before and After Polymerization
= 0% Cationic Monomer
= 12% Cationic Monomer
= 25% Cationic Monomer
Diameter (nm)
After Polymerization
Before Polymerization
Crosslinker Concentration (wt %)
Before
After

12. Crosslinked Particles Adsorbed to Surface
Low Crosslinking
High Crosslinking

13. 66K Magnification Samples Stained with 1% PTA
TEM Images of Nanogels
3% Crosslinker
12% Crosslinker
50% Crosslinker
0% Charge
12% Charge
66K Magnification Samples Stained with 1% PTA

14. Release of DNA from Non-ionic Nanogels
Initial Fluorescence
Intensity in Bag
Final Fluorescence
Intensity in Bag
Dialysis for 24 hours
at 37°C and at 4°C
Dialysis experiment:
Placed sample containing fluorescein labeled DNA in dialysis bag. Monitored the DNA diffusion out of bag over 24 hours. Used control samples of DNA without particles and DNA added to a solution containing particles. There was 4% DNA left greater than the control values after 24 hours at 37 degrees and 8% left at 4 degrees.
To extend retention time, I am preparing cationic particles.
37°C = 100%
4°C = 100%
37°C = 4%
4°C = 8%

15. Variables and Other Characteristics
Lower temperatures
Anti-freeze
Redox initiators
Hydrogen peroxide w/ ferrous ion
Surfactant free
Initiator fragment results in amphiphilic character
Micro-emulsions, Mini-emulsions
Inverse emulsions
Core-shell particles

16. Murthy N et al. PNAS 2003;100:

17. Miniemulsion Polymerization for Dually-Triggered Degradable Nanogels
Li, Z. C, et al. et al. J. Controlled Release 2011, 152, 57

19. Core-shell Polymer Particles
General Practical Uses:
impact modification (soft core, hard shell)
providing chemical reactivity to latex particles
enhancement of adhesion properties (hard core, soft shell)
controlled-release drug delivery (water-soluble core)
prevent colors from showing through (hollow core)
shell
Morphology:
core
is determined by thermodynamic control (lowest surface free energy) and kinetic control. The second polymer doesn’t necessarily form the shell!

20. Possible Morphologies
Core-shell
Inverted core-shell
Half-moon A
Half-moon B
Thermodynamically Stable Morphologies
Microdomains A B
Raspberry
Sandwich
Kinetically Trapped Morphologies
1st-stage polymer
2nd-stage polymer

21. Variables and Other Characteristics
Lower temperatures
Anti-freeze
Redox initiators
Hydrogen peroxide w/ ferrous ion
Surfactant free
Initiator fragment results in amphiphilic character
Micro-emulsions, Mini-emulsions
Inverse emulsions
Core-shell particles
pH Control
Hollow particles

22. Hollow Particles & Ropaque™
Hollow particles in: paints, sunscreens, inks, cosmetics, fluorescent coatings, forgery- or counterfeiting-proof coated paper, paper products, etc.
Hollow polymer particles industrially important
Can replace use of TiO2
Ropaque™ made by Rohm & Haas
microvoid
Raise pH
Lower pH
Kowalski, A.; Vogel, M. U.S. Patent 4,469,825.
Blankenship, R.M.; Finch, W.C.; Mlynar, L.; Schultz, B.J. U.S. Patent 6,139,961.

23. Hollow Particle Micrographs
PMMA particles via W/O/W emulsion polymerization
Core-shell hollow particles using methacrylic acid
J. Poly. Sci. A: Polym. Chem., 2001, 39, 1435
Colloid Polym. Sci. 1999, 277, 252.

24. Emulsion Polymerization for Dye-Labeled Nanoparticles
Zhu, M. Q.; Li, A. D. Q. et al. J. Am. Chem. Soc. 2006, 128, 4303

25. PGMA macroCTA as a Steric Stabiliser for the Aqueous Dispersion Polymerisation of HPMA
Y. T. Li and S. P. Armes, Angewandte Chem., 2010, 49, 4042
PGMA65
RAFT CTA
HPMA
Targeting a longer core-forming block relative to the stabiliser block
should lead to progressively larger sterically-stabilised nanolatexes?

26. Scanning Electron Microscopy Studies
Y. T. Li and S. P. Armes, Angewandte Chem., 2010, 49, 4042
105 nm PGMA65-PHPMA300 latex
90 nm PGMA65-PHPMA200 latex
SEM images confirm spherical, near-monodisperse latexes

27. Transmission Electron Microscopy Studies
Y. T. Li and S. P. Armes, Angewandte Chem., 2010, 49, 4042
PGMA65-PHPMA50
PGMA65-PHPMA70
PGMA65-PHPMA100
200 nm
Dh = 29 nm
Dh = 40 nm
Dh = 58 nm
Negative staining using uranyl formate:
Prof. S. Sugihara and Dr. A. Blanazs
Scale bar: 100 nm

28. DMF GPC Studies of PGMA-PHPMA Block Copolymers
A. Blanazs, S. P. Armes, A. J. Ryan et al., J. Am. Chem. Soc. 2011, ASAP
Aldrich-sourced HPMA has only 0.10 mol % dimethacrylate impurity
Best result: Mw/Mn < 1.20 for G47-H1000 at 99 % conv. (within 2 h at 70oC) !
So excellent control over MWD and good CTA blocking efficiencies….

29. More In Situ Studies: PGMA47-PHPMAx
Blanazs, S. P. Armes,
J. Madsen, A. J. Ryan
and G. Battaglia
JACS, 2011, ASAP
77.5 min = 68 %, DP 131
More In Situ Studies: PGMA47-PHPMAx
Scale bars: 200 nm
84 mins = 75 %, DP 150
87 mins = 78 % DP 156
75 min = 62 %, DP 123
90 mins = 82 %, DP 164
225 mins = 100 % DP 200
65 min = 46 %, DP 92 29