AKCİĞER KANSERİNE YÖNELİK TİROZİN KİNAZ İNHİBİTÖRÜ TAŞIYICI LİPİT-POLİMER HİBRİT NANOPARTİKÜLLERİN GELİŞTİRİLMESİ, KARAKTERİZASYONU VE İN VİTRO ETKİNLİĞİNİN DEĞERLENDİRİLMESİ

Abstract

Lung cancer is the top cause of cancer-related deaths for both men and women, accounting for nearly 25% of all cancer fatalities. The use of current conventional treatments for lung cancer, which lack selectivity, results in systemic toxicity, multiple drug resistance, treatment failure, and high mortality. Therefore, there is a need for new treatment approaches that are more selective, have fewer side effects, and can improve patient survival and quality of life. This thesis aims to develop and optimize lipid- polymer hybrid nanoparticulate (LPHNP) drug delivery systems, which combine lipid- based carriers with polymeric carriers, using the Box-Behnken experimental design. The goals include characterizing the optimal LPHNP formulations and evaluating their efficacy in vitro. The optimum crizotinib-loaded LPHNP formulations prepared by emulsification-solvent evaporation and nanoprecipitation method were determined to have particle size in the range of 120-220 nm, polydispersity index < 0.2, zeta potential of -10 / -15 mV suitable for passive targeting. Crizotinib was loaded into the nanoparticles with a drug loading efficiency of 70-80%. In vitro studies, IC 50 values of nanoparticles in NCI-H2228 cells were determined and it was shown that drug- loaded nanoparticles showed significant cytotoxic effect at the end of 48 hours incubation. The inhibitory effects of the formulations were assessed at the gene level using RT-PCR and at the protein level using ELISA. The formulated crizotinib-loaded lipid-polymer hybrid nanoparticles are considered to be a potentially effective treatment method for lung cancer.