Polysaccharides as a source of advanced materials: cellulose hollow microspheres for drug delivery in cancer therapy

Biocompatible hollow poly(methyl acrylic acid-co-N-isopropylacrylamide-co-ethyleneglycol dimethacrylate)@cellulose succinate (P(MAA-co-NIPAAM-co-EGDMA)@CS) microspheres have been synthesized by employing uniform silica-MPS microspheres as template. Silica spheres were synthesized via Stöber method involving tetraethyl orthosilicate. The surface of resulting silica Stöber microspheres was modified using 3-methacryloxypropyltrimethoxysilane (MPS), a polymerizable silane coupling agent. The above reagent introduces carbon-carbon double bonds on microspheres' surface. This strategy uses the copolymerization of the following monomers, methacrylic acid (MAA), N-isopropyl acrylamide (NIPAAM) and the ethyleneglycol dimethacrylate (EGDMA), which was used as cross-linker, aiming at fabricating the first shell. Distillation precipitation polymerization method was carried out with 2,2-azobis(2-methylpropionitrile) as initiator in acetonitrile aiming at coating the inorganic microspheres with organic shell of the above-mentioned copolymer. In continuation, cellulose succinate and cellulose powder was absorbed through electrostatic interactions onto microspheres' surface and the isolated product was cross-linked through esteric bonds formation. The cellulose succinate hollow microspheres were obtained after the silica core removal. The resulting spheres were characterized by Fourier transform infrared spectroscopy and observed by scanning and transmission electron microscopy. Dynamic light scattering was used to study the hydrodynamic diameter of the synthesized microspheres. The anticancer drug daunorubicin was loaded in the spheres, and its release behavior was evaluated at acidic and slightly basic pH conditions, aiming at evaluating its behavior at the healthy and pathogenic tissues.