Akademik Veri Yönetim Sistemi
MACROMOLECULES, cilt.49, sa.10, ss.3856-3868, 2016 (SCI-Expanded)
In this study, we designed, synthesized, and characterized a novel pH- and redox responsive nanoparticle system for the enhanced spatial delivery of hydrophobic drugs. A statistical copolymer library of pyridyldisulfide ethyl methacrylate (PDSM) with different compositions of 2-((tert-butoxycarbonyl)(2-((tert-butoxycarbonyl)amino)ethyl)amino)-ethyl methacrylate (BocAEAEMA) was synthesized using the reversible addition fragmentation chain transfer (RAFT) polymerization process. The controlled nature of the radical polymerization was demonstrated by a kinetic study. The Boc-groups were cleaved to obtain the desired amino functional copolymers. Nanoparticles were prepared by nanoprecipitation and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Differently sized nanoparticles that have monomodal size distributions ranging from 50 to 460 nm with positive zeta-potential values were obtained by varying initial conditions of the formulations. The pH- and redox responsiveness of the nanoparticle systems was investigated by the DLS and zeta-potential measurements. The pH-responsiveness test results demonstrated that the obtained nanoparticles reveal a pH response, such as changes in the size and zeta-potential values upon pH value change. Moreover, redox responsiveness tests revealed the stability of the nanoparticles at a glutathione (GSH) concentration found in the plasma of the human body (10 mu M) and the disassembly ability of the nanoparticles in a mimicking intracellular reductive environment (10 mM GSH). The antitumor drug doxorubicin (DOX) was used to investigate the encapsulation and release capability of the nanoparticles. Release studies showed that the DOX release was significantly accelerated in the presence of 10 mM GSH compared to the physiological conditions. Confocal laser scanning microscopy (CLSM) studies indicated that DOX-loaded nanoparticles were taken up efficiently by HEK cells, and DOX was released from the nanoparticles and interacted with the chromosomes in the cell nuclei after 6 h. Cytotoxicity tests revealed that DOX-loaded nanoparticles decreased the cell viability in a concentration and time dependent manner comparable or even better as the free DOX, whereas pure particles are biocompatible.