Design of intelligent nanoparticles for use in controlled release


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2009

Öğrenci: BANU BAYYURT

Danışman: VASIF NEJAT HASIRCI

Özet:

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‘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.