Preparation And Research On SMMC7721 Cells Absorption Of Folate-conjugated Bovine Serum Albumin Nanoparticles Contains Epirubicin Hydrochloride Nanoparticles (FA-EPI-BSANPs)

Epirubicin(EPI)has been shown to have a broad spectrum of antitumor activity.However,EPI can cause a number of toxic side effects that limit its clinical applications.The side effects are due to the nonspecific targeting method of administering the drug,damaging both cancer cells and healthy noncancerous tissues during chemotherapy.This project focused on the serious side effects and non-targeting feature of EPI and prepared EPI targeting injection formulation.This work investigated the preparation process of folate-conjugated bovine serum albumin nanoparticles(FA-BSANPs)absorbing epirubicin hydrochloride(EPI)nanoparticles(FA-EPI-BSANPs),a specific-targeting drug delivery system in cancer chemotherapy.The BSANPs were prepared by desolvation as a drug carrier system and conjugated with folate to produce FA-EPI-BSANPs that specifically target tumors by cross-linking.EPI,an anticancer drug,was absorbed by this drug carrier system.The main factors affecting FA-EPI-BSANPs quality were investigated by single factor test.The influences of six experimental parameters,namely,the adsorption time,FA-BSANP solution-absorbed EPI concentration,stirring speed,FA-BSANP solution pH,degree of cross-linking,and mass ratio of FA-BSANPs to EPI,on the drug loading efficiency(DLR)and drug entrapment efficiency(DER)of FA-EPI-BSANPs were investigated via the single factor method.Moreover,the FA-EPI-BSANPs were characterized by laser light scattering;scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),differential scanning calorimetry(DSC),and thermogravimetric analysis(TG).The inhibitory rate and target ability of FA-EPI-BSANP ware mensurated by MTT method and fluorescence(FITC)modified albumin techniques,respectivley.1.The N-hydroxysuccinimide-folate content associated with BSANPs was up to 0.9757%(Wt).2.Experimental results indicated that FA-BSANPs pH played significant roles in determining the DER and DLR of the FA-EPI-BSANPs,whereas the other four factors showed insignificant effects.The DLR and DER of EPI increased with increasing adsorption time,FA-BSANP solution concentration,and pH-value,peaking at 1,750 rpm with increasing stirring speed,but decreasing thereafter.3.The optimum FA-EPI-BSANPs conditions were determined as follows:adsorption time of 8 h,an FA-BSANP solution concentration of 3.5 mg/ml,FA-BSANP solution pH of 6.0,degree of cross-linking of 30%,and FA-BSANPs-to-EPI mass ratio of 2.56.The results indicated that the optimum operation conditions were obtained with an MPS of 145.4 nm ?0.5 nm,DLR of 23.41%,and DER of 98.93%.4.The morphology of the nanoparticles was determined by SEM,and the morphology and particle size distribution of FA-EPI-BSANPs was uniform.The characterization results showed that EPI in FA-EPI-BSANPs existed in an amorphous,instead of crystalline,state.Most of the EPI was enclosed by FA-BSANPs,and a small amount was adsorbed onto the surface of the FA-BSANPs.The FA-EPI-BSANPs particles are nearly ellipsoidal.5.The results of simulate drug release showed that drug release was reach 42.6%in 24 h at the burst release phase,which up to 84.1%at 112 h longer in the slower release phase.The observed release curve indicates that the FA-EPI-BSANPs had a sustained release property.Moreover,the observed release curve was fitted with software,which indicated that the observed release model was in close agreement with the first order kinetics model,confirming the sustained release feature of FA-EPI-BSANPs.6.The stability of FA-EPI-BSANPs was mensurated by particle size changes with different temperature and time.The paeticle size of FA-EPI-BSANPs nanoparticles no significant changed within 8 h.The stability of FA-EPI-BSANPs was stable.7.The inhibitory rate of FA-EPI-BSANP was mensurated by MTT method.The inhibitory rate of FA-EPI-BSANPs for SMMC 7721 cell developed with raise of concentration and was higher than other samples.The IC50 values of FA-EPI-BSANPs and EPI were 11.5?g/ml and 18.8 ?g/ml,respectivley.8.The target ability of FA-EPI-BSANP was mensurated by fluorescence(FITC)modified albumin techniques.The uptake rate of FA-EPI-BSANPs was higher than samples without folate conjugated,and increased with increased concentration.According to the experiment results of this study,the prepared FA-EPI-BSANP was in nanoscale and evenly distributed.They also had a narrow size distribution and a significant improvement in anticancer activity.This study is considered as an experimental foundation for further research on the in vivo activity,target ability and metabolism of the drug carrier system.