In Vitro Evaluation And In Vivo Drug Release Of N-isopropylacrylamide Nanogels

N-isopropylacrylamide is the main skeleton for the preparation of thermo-sensitive hydrogels, which have a low critical solution temperature (LCST) closed to human body temperature. As drug carriers, hydrogels can control the absorption and release of drugs. For application, N-isopropylacrylamide can be introduced with some easily ionizated acid (alkali) groups such as -COOH,-NH2. They can help gels have pH and temperature double sensitivity. Other members of our group made nanogels with pH and temperature sensitivity of N-isopropylacrylamide, which was copolymerized with allylamine and sulfadiazine. The thesis carried out some following works based on the former works:⑴The cytotoxicity of the blank p(NIPAM-co-NH2) and p(NIPAM-co-SD) nanogels, free DOX, DOX-loaded nanrogels to the human ovarian cancer cells A2780 was determined by the method of MTT. The results showed that the two blank nanogels was nearly nontoxic; but they effected the cytotoxicity of DOX differently: p(NIPAM-co-NH2) nanogel hardly effected the cytotoxicity of DOX, and p(NIPAM-co-SD) nanogel can degrade the cytotoxicity of DOX.⑵DOX has red fluorescence,and the p(NIPAM-co-NH2) nanogel's affect to the ingression in cells of DOX was observed using the fluorescence microscope. DOX in the cells of the drug-loaded nanogel was obviously less than free DOX with the same concentration,in five hours;The interaction between nanogel and A2780 cells was studied initially by coupling FITC to the p(NIPAM-co-NH2) nanoge. The results showed that, p(NIPAM-co-NH2) nanogel adsorbed to the surface of the cell membrane principally, and the internalization of nanogel into cells wasn't oburseved. The results could explain that the nanogel did not affect the cytotoxicity of doxorubicin.⑶The release of DOX-loaded p(NIPAM-co-SD) nanogel in different pH mediators was studied with the method of dialysis,at 37℃. The results showed that, DOX loaded in the nanogel released more slowly than free DOX in the buffer solution of pH 7.4. The drug release in different pH mediators was obviously different, that was the slowly release in the surroundings of pH 7.4, but more fast release literally in the surroundings of pH 6.5 and 6.0.The pH response release of the drug in nanogel was excellent.⑷The blood concentration of free DOX and DOX loaded in p(NIPAM-co-SD) nanogel in wistar male rats was studied by administrating drugs into the tail vein and aspirating blood from orbital venous. The nanogel increased the blood concentration of adriamycin, but decreased the time of adriamycin existing in the blood; and it increased the bioavailability and clearance rate of adriamycin nearly one time than free adriamycin.