The thermo-sensitive hydrogels containing chitosan, hyaluronic acid and alginate as drug delivery systems

• Main Authors: Jiuan-Wen Hu, 胡濬文
• Other Authors: Jia-You Fang
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/55409548679983448567

碩士 === 長庚大學 === 天然藥物研究所 === 95 === Thermo-sensitive polymer, poly-N-isopropylacrylamide (PNIPAAm), is a 3D network macromolecule, have both hydrophile and hydrophobic moieties. It shoes a fluid form in aqueous solution as the temperature is lower than lower critical solution temperature (LCST), and becomes semisolid gel form above the LCST. Novel thermo-sensitive hydrogels composed of PNIPAAm with chitosan (CPN) and chitosan+hyaluronic acid (CPNHA) were prepared to examine their physicochemical characteristics and in vitro and in vivo drug release. Either hydrophilic, or hydrophobic drugs including nalbuphine, indomethacin and nalbuphine prodrug were used as model drugs in the in vitro drug release experiment. These thermo-sensitive hydrogels as drug delivery system showed a significantly prolonged drug release. The release rate of a hydrophilic model drug, nalbuphine, from hydrogels increased in the order of PNIPAAm > CPNHA > CPN. But the drug release from these hydrogels showed an different trend for the other drugs. Changed the percentage of chitosan and hyaluronic acid will influence the ability of controlled release. The pharmacological activity of hydrogels incorporated with nalbuphine was determined by in vivo cold ethanol tail-flick test in rats. CPN and CPNHA could prolong the analgesic period of nalbuphine without influencing the onset time. CPNHA showed the longest analgesic period of ~4 h among three hydrogels tested. The anticancer drugs which containing platinum, cisplatin and carboplatin, catched by matrix of PNIPAAm without releasing. We used Pluronic F-127 (PF) as the thermo-sensitive hydrogel to improve this phenomenon. However, the ability of controlled release was not as well as PNIPAAm. To dissolve the insufficient controlled release capability, PF was grafted alginate (AP) or added liposome (PL), and observed if phenomenon was improved. In the in vitro release study, both AP and PL showed excellent controlled release capability. In addition, we examined the efficiency of AP and PL in the in vivo intratumor study. According to the experiment, adding liposome it could significantly improve the release capability, and even achieve more a 2-fold capability when liposome was added to AP thermo-sensitive hydrogel. The results of investigates showed that the thermo-sensitive hydrogels grafted natural polymers have excellent controlled and sustained release capability.