Hybrid and hollow Poly(N,N-dimethylaminoethyl methacrylate) nanogels as stimuli-responsive carriers for controlled release of doxorubicin

Smart drug-delivery systems based on stimuli-responsive polymers are extensively studied because of their advantages in controlled release of anti-cancer drugs in response to induced stimuli. To develop a smart drug-delivery system, silica nanoparticles modified with 3-(trimethoxysilyl) propyl methacrylate (MPS) were used in inverse emulsion polymerization of N,N-dimethylaminoethyl methacrylate with N,N-methylene bisacrylamide in different amounts (MBA: 2, 4, and 8 mol%). The temperature- and pH-responsive hybrid core-shell nanoparticles were used for preparation of hollow poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) nanogels by hydrolysis of the silica cores. Fourier-transform infrared spectroscopy was used to confirm the surface modification of silica nanoparticles with MPS. Successful synthesis of the hybrid and hollow nanogels was investigated by thermogravimetric analysis, scanning electron microscopy, and transmission electron microscopy. In addition, temperature-responsivity and phase separation behavior of the hybrid and hollow nanogels were studied by UV/Vis spectroscopy. The UV/Vis spectra showed that the absorption intensity was increased with increasing MPS and MBA contents in basic conditions. The hollow nanogels showed higher swelling/deswelling ratio compared to the hybrid nanogels in acidic media (pH 3.5) and at temperatures above the volume phase transition temperature (70 °C). Some of the hybrid and hollow nanogels with different crosslinking densities were used as smart drug carriers for doxorubicin (DOX), and their release behavior were investigated at different pH (3.5 and 7.5) by UV/Vis spectroscopy. The release profiles display that release of DOX has increased in pH of 3.5, and the hollow nanogels showed lower release contents than the hybrid nanogels because of diffusion and encapsulation of DOX molecules in the hollow space. The experimental release profiles confirmed that DOX release percentage in the hybrid nanogels was more than the hollow ones, while loading capacity of the hollow nanogels was higher. The Korsmeyer-Peppas model showed the best fitting with the experimental results of DOX release from PDMAEMA carriers.