Drug Loading And Release Study Of Thermosensititive Nanogel Dispersions For Interventional Therapy Of Liver Cancer

Currently, transcatheter arterial chemoembolization is the first choice of the treatments for intermediate or advanced stage hepatocellular carcinoma. Embolization agents are of great importance to this treatment. Researchers have paid a lot of attention to the applications of polymer materials in transcatheter arterial chemoembolization, along with the development of environmental stimulus responsive polymers during the past few decades. In this thesis, we prepared drug-loaded nanogels by utilizing nanogels as drug carriers. This drug delivery system could undergo a sol-gel phase transition when the temperature changed, and it exhibited a slow and sustained in vitro drug release profile, which could meet the clinical requirements for chemoembolization agents. Main contents and results are as follows:1. Poly(N-isopropylacrylamide-co-sulfadiazine) nanogels were prepared via soap-free polymerization, and Pickering emulsion-solvent evaporation method was employed to prepare doxorubicin-loaded nanogels. Blank nanogels had an average size of 200 nm, while the average sizes of drug-loaded nanogels varied from 200 nm to 700 nm, due to their different drug loading levels. Thermosensitivity of the nanogels remained after the drug loading process. The entrapment efficiencies determined by centrifugal ultrafiltration method were above 97 %, and drug loading level was up to 12.9 wt.%. The results of TEM imaging confirmed the structure of drug-loaded nanogels, which was consist of a drug core inside and a colloidal layer outside.2. The in vitro drug release study indicated that drug could be slowly released from the drug-loaded nanogels. According to Higuchi model, the in vitro drug half life times of drug loaded nanogels with different loading levels, which were 4.7, 9.0, 12.9 wt.%, were 1556, 1706 and 2234 h, respectively. And according to Riger-Peppas model, the drug release profiles of drug-loaded nanogels with relatively low loading levels obeyed Fickian diffusion mechanism. Proved by drug release study in different pH environments, which showed no differences, this slow release of the drug could be attributed to the particular drug-drug interaction of doxorubicin. Furthermore, in extreme environments such as organic solvents, the great mass of drug encapsulated by nanogels could be released. 3. The results of the study by vial inverting with visual method showed that both blank and drug-loaded nanogels dispersions underwent a phase transition, while the pH values of the environment ranged from 6.0 to 8.0. The gelling temperatures were around 27℃, and the critical gelling concentration was 4 wt.%. The nanogels dispersions could also achieve gelling statuses after the addition of Iohexol in dispersion medium, but the gelling temperatures were higher than that of nanogels pure aqueous dispersions.In a word, doxorubicin-loaded poly(N-isopropylacrylamide-co-sulfadiazine) nanogels dispersions prepared in this thesis could undergo a sol-gel phase transition in the simulative human body environment. Also they had relative high drug loading levels and exhibited a slow and sustained drug release profile. Such a drug delivery system had the potential to be the next generation of chemoembolization agents after the drug-eluting beads.