Temperature and pH Dual Responsive Nanogels of Modified Sodium Alginate and NIPAM for Berberine Loading and Release

[Image: see text] pH- and temperature-sensitive nanogels (NGs) were prepared from sodium alginate (SA) and N-isopropylacrylamide (NIPAM), as the sensitivity at pH 5.5 and 31 °C. SA was pH-modified with glutamic acid (Glu) and ethylenediamine (EDA). The products Glu-SA (Glu-modified SA) and EGSA (EDA- and Glu-modified SA) were characterized by ninhydrin color reaction, infrared spectroscopy, and zeta potential, and the best reactant ratio was selected. Moreover, temperature-sensitive, pH-sensitive EGSA-NGs possessing a semi-interpenetrating network structure were prepared by radical polymerization using N-isopropylacrylamide. The morphology of EGSA-NGs was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The cytotoxicity test shows the low cytotoxicity and high biocompatibility of the NGs. The newly prepared NGs were also subjected to pH-sensitive temperature-sensitive in vitro drug-loading and drug-release experiments. The pH-sensitive and temperature-sensitive experiments showed that the particle size of EGSA-NGs was reduced at pH 5.5 and above 31 °C. The drug-loading and drug-release experiments also confirmed this finding, indicating that the newly synthesized NGs could release the drug according to the environmental changes. Therefore, the material has potential application value in solid tumor targeted therapy.