Beyin Glioma Tedavisinde Dosetaksel Yüklü Katyonik Nanopartiküllerin Tasarımı ve İn Vitro Değerlendi

Abstract

Brain tumor is an abnormal growth of neoplastic cells within the brain. The most common problem for treatment of brain tumors is the insufficiency of chemotherapy. Cell culture studies show that chemotherapy drugs are effective against glioma cell lines. However, the same effect didn?t occur at in vivo studies. Thus, developments of novel drug delivery strategies are necessary and nanoparticles are promising systems in this field. Polycaprolactone (PCL), which is used for nanoparticle preparation, is biodegradable, biocompatible and non-toxic polymer approved by FDA for therapeutic use. Chitosan (CS) is a linear polysaccharide. It contains cationic groups and has anticancer, mucoadhesive and immunoadjuvant effect. It is used for nanoparticle preparation as polymer or coating material. The aim of this study was to develop different polymeric nanoparticles to be applied as implants to the tumor site following surgical operation in brain glioma treatment. In this context, PCL was selected as base polymer and methoxy polyethylene glycol-polycaprolactone (mePEG-PCL) copolymers along with CS coating to render positive surface charge were used. Although the particle size of the formulations varied according to polymer type, preparation technique and other technological parameters, it varies in the range of 70 to 270 nm. This size is favorable in terms of cellular uptake and accumulation in tumor site. Modal drug Docetaxel (DOC) is highly loaded into all particle formulations. It was found that in the cell culture studies blank nanoparticles did not show any cytotoxic effect on mouse fibroblast cells, however DOC loaded nanoparticles demonstrated significantly high cytotoxic effect on RG-2 rat glioma cell line. CS-mePEG-PCL formulation in particular shows higher cytotoxicity than the drug solution itself due to its positive surface charge as well the anticancer and immunogenic effects of chitosan.