Advanced design of biocompatible stimuli-responsive nanocapsules and nanogels for antitumor drug and gene delivery

Resumo

In this PhD thesis, the synthesis and characterization of new stimuli-sensitive biocompatible and biodegradable nanogels that could be potentially useful as nanocarriers in controlled drug/gene delivery is presented. Emulsion polymerization is the polymerization process used for the synthesis of new biocompatible nanogel particles with different morphologies such as nanocapsules (hollow nanogels) and core-shell nanogels.The characterization of the nanogels and nanocapsules synthesized has been carried out by analyzing polymeric and colloidal properties. Furthermore, the stimuli-sensitivity of nanogels and nanocapsules together with their most representative parameters such as volume phase transition temperature and pH (VPTT and VPTpH) have been included.Regarding the biodegradability of the nanogels synthesized, the capability to absorb dextranase enzyme for several nanogel particles has been studied. In addition, the enzymatic degradation of these nanogel particles using different dextranase activities has been analyzed.With respect to drug/gene delivery applications, the suitability of nanogels selected as potential carriers for two interesting cargo molecules such as Doxorubicin and small interfering RNA (siRNA) has been validated. Furthermore, in some cases, cell internalization and cargo delivery routes have been studied using cervical HeLa and breast cancer MDA-MB-231 cell lines.