Synthesis, characterization, and preliminary application of new biocompatible nanogels useful as anticancer drug delivery systems

Abstract

In this PhD thesis, the synthesis, characterization, and preliminary bio-applications of new nanogels and magneto-nanogels, are presented. Different families of cationic nanogels based on poly(diethylaminoethyl methacrylate) were synthesized by surfactant-free emulsion polymerization. The nanogels obtained were able to undergo large reversible volume changes in response to pH and temperature. The effect of different synthesis variables such as the initiator, stabilizer, and comonomer concentrations, and type and concentration of the cross-linker on the response to pH and temperature, and on the inner morphology of the nanogels, was studied. It is remarkable that these nanoparticles showed stimuli-responsiveness at physiological conditions (38 °C and pH 7.1). Different families of magneto-nanogels were also prepared by encapsulating magnetic nanoparticles into the previously synthesized nanogels. In addition to the stimuli-responsiveness, the magneto-nanogels showed superparamagnetism. With the aim of studying the suitability of these nanoparticles for biomedical applications, preliminary studies on their biocompatibility were carried out: cytotoxicity tests for some nanogels using a HeLa cell line were performed and the biocompatibility of the magneto-nanogels with human blood cells was validated. Moreover, it was demonstrated that some nanogels synthesized were able to encapsulate large amounts of the antitumor drug Doxorubicin due to the formation of hydrogen bonding between the drug and the polymeric chains of the nanoparticles. The drug was released by diffusion. It must be highlighted that the drug release from the nanogels was faster at acidic conditions due to the swelling of the nanoparticles, increasing their potential as antitumor drug delivery systems since the extracellular pH of unhealthy cells and tissues is more acidic than that of the healthy ones. The cellular internalization of the drug loaded-nanogels in MDA-MB-321 cell line was also demonstrated.