| Due to the poor solubility,short half-life and toxic side effects of anti-tumor drugs,researchers are gradually focusing on the delivery process of drugs.At this time,nanotechnology emerge and is widely used to construct nanodrug delivery systems.Bovine serum albumin?BSA?is commonly used as a drug carrier,because of its unique physical and chemical properties.It has manyadvantages,such as maintaining osmotic pressure,pH buffer,carrier and nutrition supplement.20?R?-Rg3,as a model drug,which has good anti-tumor effect.Although 20?R?-Rg3 possesses a variety of medically beneficial effects,the clinical application is restricted due to its poor water solubility and short circulation half-life and bad target specificity into tumour tissues.BSA was selected as the nano-carrier in this study,andmethoxy polyethylene glycol succinate?mPEG-SA?was a modifier,and mPEGylation-Rg3-BSA nanoparticles were prepared by desolvation method.The results showed that the nano drug delivery system improve solubility and bioavailability,and realize the sustained release of drug and improve the anti-tumor effect.Firstly,the optimum technological conditions were obtained by single factor experiment:the concentration of BSA was 20 mg/mL,the pH value of the solvent was 9,the stirring speed was 500 r/min,and the volume ratio was 1:3,absolute ethanol was added to the BSA nanoparticles by 0.5 mL/min,and the reaction time was 24 h.The nanoparticles were generally spherical in shape with a narrow size distribution,the mean particle size and PDI of the mPEG-Rg3-BSA nanoparticles were 194.3 nm and PDI=0.214,respectively.Secondly,the mPEG-Rg3 was prepared by esterification.The FTIR spectrum of the mPEG-Rg3 conjugate contains all expected resonance peaks characteristic of mPEG-SA and Rg3,the characteristic peak?C=C=C and?C=O at 1630 and 1728 cm-1,respectively.The extent of mPEG-SA conjugation was calculated based on the ester bonds of mPEG-Rg3 at 172.18 ppm and 169.38 ppm.The prepared mPEG-Rg3-BSA nanoparticles were generally spherical and uniformly dispersed.In addition,drug model release was tested at pH=7.4,when released time was less than 40 h,the changes of drug release is quite obvious,and then with the extension of time,the changes was slow down at 120h and tended to be stable;The anti-tumor effect of drug delivery system on the growth and proliferation of cancer cells was studied by cytotoxicity experiments.Results showed that nano-drug delivery system has higher anti-tumor activity than free drug,and the cell inhibiting rate of it was better to HepG-2 cells.The uptake of nanoparticles by HepG-2 cells and L929 cells was observed.The results showed that nanoparticles entered the cytoplasm and were more selective to tumor cells than normal cells.Hoechst 33342staining showed that the nano-drug delivery system induced cell apoptosis more strongly than the free drug.In vivo imaging experiments showed the distribution of drug in the main organs of nude mice,we concluded that the hydrophilic corona of the nanoparticles could significantly prolong the nanoparticles blood circulation,which was beneficial for the nanoparticles to achieve an EPR effect.Thus,the passive targeting ability of the nanoparticles to the tumor site was preferable... |
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