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

Abstract

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 semiinterpenetrating 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 drugloading 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.

Current Research on Polyelectrolyte Nanostructures: From Molecular Interactions to Biomedical Applications

“…The LCST of the NGs was 31 °C. Therefore, two volume phase transitions were poss ble in this system [51].…”

“…Ethylenediamine and glutamic acid groups were added to alginate resulting to an isoelectric point of the NPs at 5-5.5. The LCST of the NGs was 31 • C. Therefore, two volume phase transitions were possible in this system [51].…”

Strategic Design of Intelligent-Responsive Nanogel Carriers for Cancer Therapy

“…It is necessary to invent a combination of treatment and diagnosis methods since the cancer can hardly be diagnosed in advance and predicted the case path . Multistimuli-responsive nanogels play important roles in the combined treatment of tumors, such as chemotherapy, photodynamic, photothermal therapy, cancer starvation, and oxidation therapy. − Nanogels exhibit uncontrollable release or unintelligent release behaviors. Nanogels with a single stimulus response have the limitations as mentioned previously, including single function, uncontrollable, and unintelligent release behavior.…”

“…Thermal/pH stimuli-responsive nanogels are suitable for external heating-chemotherapy combination therapy without domino effective trigger. − Pruettiphap et al explored a thermal/pH-responsive nanogels based on NIPAM and acrylic acid (AA) through differential microemulsion polymerization . The morphologies (hairy microgels or core–shell morphology) and LCST (6 or 27 °C) of the poly­(NIPAM- co -AA) nanogels were controlled by adjusting the monomer contents.…”

Synthesis and Characterization of a Novel Dual-Responsive Nanogel for Anticancer Drug Delivery

“…By simultaneously using temperature and pH-responsive monomers in the nanogel structure, dual-responsive systems can be created which have controlled drug release behavior in the cancerous site. Recently, Chang et al synthesized pH and temperature-responsive nanogels based on sodium alginate with the natural pH sensitivity and PNIPAAm as a temperature-sensitive polymer [ 35 ]. They modified sodium alginate by glutamic acid and ethylenediamine to change its charge distribution to achieve desire pH sensitivity.…”