Responsive nanogels for application as smart carriers in endocytic pH-triggered drug delivery systems

• Poly(NIPA-co-AAc) NGs were prepared in different composition of NIPA/AAc.
• NG presented excellent dispersability at pH 7.4 and 5 at 37 °C.
• The NGs were non cito-toxic for models cells.
• NGs present high drug loading capacity and efficiency of DOXO·HCl.
• A minimal leakage of DOXO·HCl at pH 7.4 and a triggered release at pH 5 was observed.

Various specially designed poly(N-isopropylacrylamide-co-acrylic acid) (NIPA-co-AAc) nanogels (NGs) with different NIPA/AAc molar composition were synthesized by precipitation/dispersion polymerization and evaluated as carriers for drug delivery systems (DDSs) of doxorubicin hydrochloride (DOXO·HCl) for cancer therapies. The NGs presented excellent dispersability in physiological environments (pH 7.4 and 5 at 37 °C), as shown by dynamic light scattering (DLS). Moreover, the NGs exhibited high drug loading capacity and efficiency due to the ionic interaction of the cationic drug with the anionic NGs. NG-DOXO·HCl formulation presented excellent dispersability in water and minimal leakage of the cargo at plasma simulated medium (pH 7.4 and 0.14 M NaCl) at 37 °C and a triggered release at lysosomal simulated medium (pH 5 and 0.14 M NaCl). This release behavior together with their size and the low cytotoxicity determined by the MTT assay converts these NGs in great candidates for their application as carriers in cancer therapies based on the enhanced permeability and retention effect (EPR) with drug pH-triggered release after endocytosis in tumor cells.

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