The aim of this project was to design an intelligent controlled release system
based on thermoresponsive nanoparticles for cancer therapy and to evaluate
the efficiencies of these systems with in vitro cell culture. Poly(Nisopropylacrylamide),
an important thermoresponsive polymer, was selected
for this study to prepare the responsive nanoparticles. This polymer has an
lower critical solution temperature (LCST) of 32 oC, below which it is
hydrophilic and above this temperature, it shows hydrophobic behavior.
Controlling drug release with this property was the objective of this study.
Nanoparticles were prepared by nanoprecipitation method. By using different
solvent:non-solvent ratios and polymer concentrations, different samples
were prepared. The particle size was decreased when solvent:non-solvent
ratio was increased and polymer concentration was decreased. This was found
to be related with the solution viscosity.
Nanoparticles prepared from polymers prepared with different initiatoraccelarator
amounts had significantly different sizes and release rates, and
additionally the size of particles prepared from polymers with various
crosslinker amounts were decreased with increased croslinker amount.
In situ release experiments were performed both below and above polymer& / #8216 / s
LCST degree. Uncrosslinked nanoparticles demonstrated higher release rate of
Celecoxib above LCST. However, there was no significant difference with the
crosslinked nanoparticles.
Crosslinked and uncrosslinked nanoparticles were tested on Saos-2 cells to
assess their toxicity. Both Celecoxib loaded and free crosslinked particles were
found to be cytotoxic. Uncrosslinked nanoparticles showed an increased
toxicity upon loading with the bioactive agent, Celecoxib. In conclusion,
uncrosslinked particles would be a proper drug carrier for cancer therapy with
enhanced drug loading.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/3/12610515/index.pdf |
| Date | 01 March 2009 |
| Creators | Banu, Bayyurt |
| Contributors | Hasirci, Vasif |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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