Beyı̇ne Hedeflendı̇rı̇Lmı̇Ş Bevası̇ Zumab YüKlü Nanopartı̇KüLer İLaç TaşIyıcı Sı̇Stemlerı̇N Hazırlanması Ve Etkı̇nlı̇Klerı̇nin Değerlendı̇rı̇Lmesı̇

Abstract

In this study, in order to target Bevacizumab to the brain, PLGA-PEG nanoparticles conjugated with Anti-CD71 antibodies that bind specifically to transferrin receptors known to be expressed in the blood-brain endothelium were prepared. In the conjugation step, synthesized OCA molecule was used. As the control groups of the anti-CD71 antibody conjugated nanoparticles, nanoparticles conjugated with Isotype Control antibodies, which are the same as Anti-CD71 but not specific to the receptor, were used. Bevacizumab was loaded into actively targeted nanoparticles to evaluate encapsulation efficiency and release properties. Cell culture studies were performed on bEnd.3 and hCMEC / D3 endothelial cells and U87 glioma cells. The cytotoxicity of the drug delivery system prepared in these three cell lines was investigated and the binding affinities of antibodies and antibody conjugated nanoparticles to TfRs on the surface of these cells were investigated. In the transition phase of the blood-brain barrier, intake studies were carried out with bEnd.3 and hCMEC / D3 cells, in which the receptor-mediated endocytosis of the drug delivery system would occur, and the in vitro passage of bevacizumab through the blood-brain barrier was demonstrated with the monoculture transcytosis experiments. The passage of Nile red loaded nanoparticles across the blood brain barrier was investigated by in vivo experiments and demonstrated by fluorescence microscopy. An in vivo GBM model was developed in nude mice and the efficacy of drug loaded control groups and drug loaded Anti-CD71 antibody conjugated nanoparticle groups were compared. The group of mice loaded with bevacizumab and given actively targeted nanoparticles survived longer than other groups of mice.