1. Temperature sensitive nanogels for drug delivery and
methods to improve nanoparticle recovery
Sarah Hutchinson, Jonathan T. Peters, and Nicholas A. Peppas
Department of Chemical Engineering, Department of Biomedical Engineering
Biomaterials, Drug Delivery and Regenerative Medicine
The University of Texas at Austin, Austin, TX 78712
Targeted Drug Delivery
Solubility of fluorescein and PNIPMAAm/PPhMA Challenges/Future Work
Introduction and Scope of Work
Thermoresponsive nanogels
Temperature sensitive polymers improve drug efficiency
by facilitating delivery to targeted area within a desired
concentration and time interval.
Nanogels such as Poly(N-isoproyl acrylamide)
(PNIPAAm) entrap drugs and act as nanocarriers.
PNIPAAm encapsulates and carry drug to target tumor
cells.
EPR facilitates retention of encapsulated drug in tumor
vasculature.
Surface modifications increase LCST ≈ 40 °C
After reaching target tumor cells, an external stimulus:
 Heats PNIPMAAm above LCST
 Collapses nanogel network
 Forces drug out
Objective
The current challenge is determining a reproducible and
convenient methods for drug loading that will achieve
high entrapment and nanoparticle recovery.
 EtOH has shown high solvent volumes to dissolve
PNIPMAAm/PPhMA
 DMF dissolves polymer moderately but current
dialysis bags (Spectra/Por Regenerated Cellulose)
have limited exposure.
 Future work is to measure the effectiveness of
dialysis to load therapeutic drugs.
Determine drug loading efficiency of
fluorescein in the PNIPMAAm/PPhMA (per
solven)
Determine the nanopartical yield
1. Na, K., Hee Lee, K., Haeng Lee, D., & Han Bae, Y. (2006). Biodegradable thermo-sensitive
nanoparticles from poly(lactic acid)/poly(ethylene glycol) alternating multi-block copolymer for
potential anti-cancer drug carrier. European Journal of Pharmaceutical Sciences, 27, 115-122.
2. Lyon, A. L. (n.d.). “Smart Nanoparticles” stimuli sensitive
hydrogel particles. Lecture presented at Georgia Institute of Technology.
3. Zhang, Z., & Feng, S.-S. (2006). Self-assembled nanoparticles of poly(lactide)-Vitamin E TPGS
copolymers for oral chemotherapy. International Journal of Pharmaceutics, 324, 191-198.
4. Sanson, C., Christophe, C., Le Meins, J., Soum, A., Thevenot, J., Garanger, E., &
Lecommandoux, S. (2010). A simple method to achieve high doxorubicin loading in
biodegradable polymersomes. Journal of Controlled Release.
http://10.1016/j.jconrel.2010.07.123
Acknowledgements
I want to thank my research mentor Jonathan Peters for teaching me about his
research and encouraging me to ask questions that would help me design my own
experiment.
References
Stimulus
PEG
Tumor cells
PNIPMAAm
gel network
Drug
T>LCST
Problematic Drug Release
Toxic Level
Desirable –
Controlled Release
Minimum effective
level
TimeStimulus
Solvent Testing
Experiment
Compare the drug loading efficiency and nanoparticle recovery
between three solvents via dialysis. Dialysis is a drug loading
technique that is simpler than other methods because it avoids
stabilizers and emulsifiers. Fluorescein was substituted for the
doxorubicin and PNIPMAAm/PPhMA (core/linker) was used for
nanoparticle
EtOH DMSO DMF
Methods
1) Test solubility of
fluorescein in
solvents by adding
solvent to known
amount of
fluorescein.
EtOH DMSO DMF
EtOH DMSO DMF
1:100 NP:fluroescein
1:10 NP:fluroescein
1:1 NP:fluroescein
2) For each solvent test
three ratios of NP to
fluorescein
3) Dialyze each
homogenous solution
against filtered water
Synthesis of Thermo-responsive nanoparticles
Ammonium Persulfate
(APS)
Initiator
NIPAAm N’N’-Methylene-bis-
acrylamide
(MBAAm)
Sodium dodecyl sulfate
(SDS)
Monomer SurfactantCrosslinker
Inject APS/water
solution
and react for 6 hours
Dialysis against
water for 3 weeks
Dissolve NIPMAAm
MBAAm, SDS in filtered
water in round bottom flask
Heat solution to 70 °C in
an oil bath and N2 purge
for 30 min
(presence of O2 stops
reaction)