Controlled delivery of drugs through smart pH-sensitive nanohydrogels for anti-cancer therapies: Synthesis, drug release and cellular studies

Nanohydrogels were synthesized by microemulsion polymerization. These nanohydrogels were pre-designed to be pH and temperature stimuli-response materials, using N-isopropylacrilamide as a base monomer and 1-vinyl imidazole as ionizable comonomer. The pH sensitivity was confirmed by measuring the increase or decrease in volume in the nanoparticles by changing the pH of the medium. Nanoparticles were properly characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM). Glass-transition temperature increased with vinyl imidazole content, and nanoparticles with average diameter of 68 nm were obtained. Particle size decreases with the increase in pH. After characterization, nanohydrogels were functionalized with folic acid to take advantage that the folate receptor is overexpressed in different types of cancer cells. The nanoparticles were loaded with the drugs: metformin, terfenadine, and 5-fluorouracil. The amount of drug loaded and released by nanoparticles was measured by UV-vis spectroscopy. Then, cellular viability and internalization studies were performed obtaining promising results.