ABSTRACT
DDP could be easily incorporated into poly (?-glutamic acid)-D-galactose esterifiable derivative through a covalent bond. The yield of DDP incorporation into the ?-PGA was 9.4%～10.2%. The DDP was released in the initial 8h in a burst manner,and thereafter in a sustained manner. The results that the conjugation of DDP to poly (?-glutamic acid)-D-galactose esterifiable derivative not only reduced the toxicity of the DDP but also enhanced antitumor activity and the targeting ability. The vivo experiments conclusively established that the ?-D+-DDP compound was much less toxic to animals than DDP alone. A direct evaluation showed that mice treated with ?-D+-DDP compound at a dose of 7.5 mg/kg displayed significant tumor regression. Furthermore,the implanted solid tumors disappeared completely from 35% of the H22 tumor-bearing mice after ?-D+-DDP compound administration. The aforementioned results of biodistributions of the prepared ?-D+-DDP compound in various organs in normal mice demonstrated that the ?-D+-DDP compound had a specific interaction with liver's parenchymal cells and H22 hepatocellular carcinoma tumor cells via ligand receptor recognition. In conclusion,the results indicated that the ?-D+-DDP compound prepared can effectively target the site of hepatoma tumor via the recognition and significantly reduce its size. The ?-D+-DDP compound was less toxic than the free DDP,and could effectively reduce xenografted H22 hepatocellular carcinoma cells in KM mice and prolong the survival of KM mice grafted with H22 hepatocellular carcinoma tumor cells. Therefore,the prepared ?-D+-DDP compound may be used as a potential drug delivery system for the targeted delivery to liver cancers or other liver diseases.
ABSTRACT
The study was to develop cis-dichlorodiammineplatinum(DDP)-loaded formulations using a novel type of self-assembled compound composed of block copolymers synthesized by poly(?-glutamic acid)(?-PGA).For the potential of targeting liver cancer cells,D-galactose was conjugated on the prepared ?-PGA.In vitro,DDP can be released from the resulting conjugate in PBS:there was a burst release during the first 8 h,then followed by sustained release.DDP could be easily incorporated into poly(?-glutamic acid)-D-galactose esterifiable derivative through a covalent bond.The yield of DDP incorporation into the esterifiable derivative was 9.4%～10.2%.In vitro experiments conclusively established that the poly(?-glutamic acid)-D-galactose esterifiable derivative-Cisplatin Complex Compound(?-D+-DDP)was much less toxic to normal cell lines than DDP only.The surviving rate of cells treated with ?-D+-DDP compound is higher than those treated with free DDP.Also it has obvious antitumor efficiency on human liver tumor BEL-7402 cells.HE staining indicated that the ?-D+-DDP compound make the BEL-7402 apoptosis.These results indicated that the conjugation of DDP to the esterifiable derivative reduced its cytotoxicity activity,but retains its antitumor activity in vitro.In conclusion,the ?-D+-DDP compound could be used as a potential clinic antitumor drug.The ?-PGA obtained by fermentation can be used as a valuable drug carrier system.
ABSTRACT
This thesis aimed at the Bacillus natto TK-1 screened out from Natto.The lipopeptide was purified using Thin-Layer Chromatography(TLC),and investigated its anti-tumor activity.After acid precipitation and methanol extraction,the lipopeptide was separated on TLC.Then the authors get the monomer surfactin which molecular weight is 1036Da through the High performance liquid chromatography(HPLC),electro spray ionization-mass spectrometry(ESI-MS) and infrared(IR).MTT method was implied to testify the anti-tumor activity of the purified sample from TLC.The results indicated a concentration and time-dependent relationships.After 48h,their IC50 were 40 mg/L.The detection with inverted microscope fluorescence microscope displays that the surfactin will cause a series of Morphological changes to the cells.In TUNEL experiment,the authors noticed that surfactin has the ability to induce apoptosis,besides this inhibition shows an obvious time-dependent relationship.