Exploring the Rheological Properties of 

Dense Lipid Vesicle Solutions as Models for 

Liposome Nanomedicines

By: Emily Blick
PRESENTATION OVERVIEW

• Background

• What are liposomes?

• Why do we care?

• My Project

• Rheology experiment

• Stability experiment

• SANS 

• Summary of Conclusions

• Future Work
WHAT ARE LIPOSOMES?

• Lipids are amphiphilic molecules

• Lipids in solution form liposomes

• Enclose aqueous solutions

• Using model system 1,2-Dioleoyl-snglycero-3-phosphocholine (DOPC)

• Commonly used lipid in research

• Relatively inexpensive

Hydrophilic head group

Hydrophobic tails

Hydrophilic Hydrophobic
WHY LIPOSOMES?

• Liposomes are promising candidates for future drug delivery applications

• Similar morphology to the cellular membrane

• Biocompatible, biodegradability, and low toxicity

• Nanomedicine possibilities

• Liposomal nanomedicines can be designed to accumulate at sites of 

disease

• Possibilities for cancer treatment and vaccine development! New cancer drug!
RHEOLOGY-THE STUDY OF 

FLOW OF MATTER

• Liposome therapeutics will likely be 

delivered through a syringe

• Solution will experience shear stress going 

through needle

• How does concentration and shear rate 

affect solution viscosity?

• How can we predict volume fraction of 

liposomes?

vv(t) F

F

More viscous sample
RHEOLOGY EXPERIMENT

• Measurements were taken using a 

rheometer

• Measures torque response of solution to an 

applied force

• Calculate viscosity

• Made concentration series to study 

relationship between concentration and 

viscosity

• Better estimate volume fraction Sample

Rotating geometry

Torque
VOLUME FRACTION 

CALCULATIONS

Will allow better prediction of volume fraction for 

future experiments!

ηη

ηη0

= 1 + 2.5φφ Relative 

Viscosity

Specific ηηssPP

= ηηrr − 1 = 2.5φφ Viscosity

y = 0.025x + 8E-17

0

0.05

0.1

0.15

0.2

0.25

0 2 4 6 8 10

Relative Viscosity

Diluted φφ

Relative Viscosity vs. Volume Fraction

0.8

0.85

0.9

0.95

1

1.05

1.1

1.15

0 100 200 300 400 500

Viscosity [mPa·s] 

Shear Rate [1/s]

Viscosity vs. Shear Rate

DI WATER

8X

6X

5x

4x
STABILITY

• What factors impact long term stability of 

vesicle system?

• Temperature?

• Size?

• Concentration?

• What happens to DOPC liposomes when 

they become unstable at different 

conditions?

• Multilamellar?

• Aggregation?

• ?

• What are the consequences for drug 

delivery?

• Generally assumed DOPC stable at high 

concentration for about 2 weeks

• No known data supporting

unilamellar

multilamellar

aggregation

?
DYNAMIC LIGHT SCATTERING

• Popular light scattering technique 

• Laser beam shot at sample and detector 

senses changes in scattering light

• Particles scattered at known angle

• Can provide diffusion coefficient 

• Can be related to particle size

• Only valid at low concentrations

Radius!
STABILITY EXPERIMENTS

• Set up 5 vials at different concentrations at three different 

temperatures

• Concentrations: 50, 25, 12.5, 5, 1 (mg/mL)

• Set up conditions with a diameter of 60, 100, 120, 200 nm

• Took frequent DLS measurements

• Each sample under the same conditions during measurement

4°C 22°C 55°C
STABILITY RESULTS FOR 200 NANOMETER VESICLES

°C

°C

°C

80

90

100

110

120

130

140

0 5 10 15 20

avg radius(nm)

days

25(mg/mL)

40

60

80

100

120

0 5 10 15 20

avg radius(nm)

days

1(mg/mL)

50

100

150

200

250

0 5 10 15 20

avg radius(nm)

days

50(mg/mL)

50

70

90

110

130

150

0 5 10 15 20

avg radius(nm)

days

5(mg/ml)

Summary:

• Samples at lower 

temperature:

• Follow similar mostly 

flat path

• Samples at high 

temperature:

• Show unpredictable 

pattern
STABILITY RESULTS FOR 120 NANOMETER VESICLES

°C

°C

°C

50

100

150

200

250

0 5 10 15

avg radius(nm)

days

50(mg/mL)

50

60

70

80

90

0 5 10 15

avg radius(nm)

days

25(mg/mL)

50

60

70

80

90

0 5 10 15

avg radius(nm)

days

5(mg/mL)

30

50

70

90

0 5 10 15

avg radius(nm)

days

1(mg/ml)

Summary:

• Samples at lower 

temperature:

• Follow similar mostly 

flat path

• Samples at high 

temperature:

• Show unpredictable 

pattern
STABILITY RESULTS FOR ROOM TEMPERATURE

0

20

40

60

80

100

120

0 5 10 15 20 25

avg radius (nm)

days

50(mg/mL)

0

20

40

60

80

100

120

0 5 10 15 20 25

avg radius (nm)

days

25(mg/mL)

0

20

40

60

80

100

0 5 10 15 20 25

avg radius (nm)

days

5(mg/mL)

0

20

40

60

80

100

0 5 10 15 20 25

avg radius (nm)

days

1(mg/mL)

°

°

nm

nm

nm

nm

Summary:

• Samples at room 

temperature:

• Follow same path at 

22°C and 4°C

• Path continues 

almost flat for all 

vesicle sizes
STABILITY RESULTS FOR 55

°C

0

50

100

150

200

250

05 10 15 20

avg radius (nm)

days

50(mg/mL)

0

50

100

150

05 10 15 20

avg radius (nm)

days

25(mg/mL)

0

50

100

150

05 10 15 20

avg radius (nm)

days

5(mg/mL)

0

20

40

60

80

100

120

05 10 15 20

avg radius (nm)

days

1(mg/mL)

°°

nm

nm

nm

nm

Summary: • Samples at 55

°C :

• Different and 

unpredictable

• Maintain 

unpredictability at all 

vesicle sizes

• Lower concentration 

of 1(mg/mL) shows 

pattern of decreasing 

vesicle size
0.1

1

0 500 1000 1500 2000 2500 3000 3500

log((g1(t))

Time(μs)

1(mg/mL) at 55°C-Raw Data 

Day One Day Eight Day Nineteen

Day 8

RAW DATA

Day 1

Day 19

Type equation

here.

0

20

40

60

80

100

120

0 5 10 15 20

average radius (nm)

days

1(mg/mL) at 55°C

°

°

nm

nm

nm

nm
SMALL ANGLE NEUTRON SCATTERING

• Probes material structures by interacting with nucleus in sample

• Neutron scattering occurs due to the scattering length density 

components in sample

• Scattering vector Q can tell us about structures in our sample

Neutron beam

Sample

Scattered beam

Detector

Q
SANS 100 NANOMETER RESULTS

φφ=1%

φφ=5%

φφ=15%

φφ=30%
SANS 50 NANOMETER RESULTS

φφ=1% φφ=5%

φφ=15%

φφ=30%
CONCLUSION

• The possibility of liposomes for nanomedicines is dependent on vesicle stability 

and rheological properties

• What I completed:

• Created a model to estimate volume fraction based on sample viscosity to 

improve future experiments

• Ran multiple stability tests showing DOPC instability at high temperatures

• Completed SANS experiment showing temperature dependence

• Defies what is generally assumed
FUTURE WORK

• Study the possibility of chemical decomposition 

• Analyze spin echo data

• Continue trials on smaller vesicles

• Continue trials in higher concentrations but dilute right before 

measurements

• Run RheoSANS experiment in relation to future injection applications

• Run SANS experiments on samples after duration of time at different 

temperatures
ACKNOWLEDGEMENTS

• My mentor Yun Liu

• Zhenhuan (Michael) Zhang

• NCNR SURF Directors: Julie Borchers and Joe Dura

• Brandi Toliver

• Center for High Resolution Neutron Scattering

• NIST Center for Neutron Research

• My fellow NCNR SURFers
REFERENCES

• https://www.ncbi.nlm.nih.gov/pubmed/18095927

• https://lsinstruments.ch/en/technology/dynamic-light-scattering-dls/

• https://www.eeht.org/journal/view.php?year=2014&vol=29&no=1&spage=e2014016

• https://www.eeht.org/journal/view.php?year=2014&vol=29&no=1&spage=e2014016

• http://soft-matter.seas.harvard.edu/images/1/1a/Cone_and_plate.jpg