AUTHOR=Wang Wei-Jie , Huang Yin-Chou , Su Chao-Ming , Ger Tzong-Rong 

TITLE=Multi-Functional Drug Carrier Micelles With Anti-inflammatory Drug

JOURNAL=Frontiers in Chemistry

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00093

DOI=10.3389/fchem.2019.00093

ISSN=2296-2646

ABSTRACT=<p>The multi-functional micelles poly(<italic>N</italic>-isopropylacrylamide-<italic>co</italic>-<italic>N</italic>,<italic>N</italic>-dimethylacrylamide-<italic>co</italic>-10 undecanoic acid)/CM-Dextran Fe<sub>3</sub>O<sub>4</sub> (PNDU/CM-Dex Fe<sub>3</sub>O<sub>4</sub>) were poly (NIPAAm-<italic>co</italic>-DMAAm-<italic>co</italic>-UA) (PNDU) grafting hydrophilic CM-Dextran Fe<sub>3</sub>O<sub>4</sub> which possess pH-dependent temperature response and magnetic response. In this research, anti-inflammation drug Hesperetin was encapsulated by micelles using membrane dialysis method to obtain the different ratio of Hesperetin-embedded P<sub>5</sub>DF<sub>10</sub>, P<sub>10</sub>DF<sub>10</sub>, and P<sub>20</sub>DF<sub>10</sub>. These micelles were characterized by Fourier transform infrared spectroscopy, <sup>1</sup>H-NMR, thermogravimetric analyzer, and superconducting quantum interference device magnetometer. The morphology and particle size of micelles was observed by transmission electron microscopy and dynamic light scattering. The low critical solution temperature of the P<sub>10</sub>DF<sub>10</sub> micelles is in pH 6.6 at about 37.76°C and in pH 7.4 at about 41.70°C. The biocompatibility of micelles was confirmed by cytotoxicity study. Inflammatory inhibition of hesperetin-embedded P<sub>10</sub>DF<sub>10</sub> micelles also studied through RAW264.7. Hesperetin-embed P<sub>10</sub>DF<sub>10</sub> micelles suppressed LPS-induced inflammatory response. Via immunofluorescence cell staining demonstrate that Hesperetin-embed P<sub>10</sub>DF<sub>10</sub> micelles inhibited the activation of NF-κB p60 and markedly attenuated in a drug dose-dependent manner. At a concentration of 1,000 ug/ml, an inflammatory rate can be reduced to 36.9%. Based on these results, the hesperetin-embed P<sub>10</sub>DF<sub>10</sub> micelles had successfully synthesized and enable to carry and release the anti-inflammatory drugs, which instrumental for biomedical therapy and applications.</p>