PREPARATION OF FOLATE-CONJUGATED BOVINE SERUM ALBUMIN NANOPARTICLES ADSORBING EPIRUBICIN HYDROCHLORIDE

This work investigated the preparation process of folate-conjugated bovine serum albumin nanoparticles (FA–BSANPs) adsorbing 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 adsorbed by this drug carrier system. The influences of six experimental parameters, namely, the adsorption time, FA–BSANPs solution-adsorbed EPI concentration, stirring speed, FA–BSANPs solution pH, the ratio of glutaraldehyde and BSA, 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. The results indicated that the optimum operation conditions were obtained with 145.4 nm±0.5 nm MPS, 23.41% DLR and 98.93% DER. The N -hydroxysuccinimide-folate content associated with BSANPs was up to 0.9757% (wt). The DLR and DER of EPI increased with increasing adsorption time, FA–BSANPs solution concentration, and pH value, peaking at 1750 rpm with increasing stirring speed, but decreasing thereafter. The FA–EPI–BSANPs obtained were characterized by laser light scattering, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and thermogravimetric analysis. Drug release in vitro was investigated, as well. 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 and significantly affect sustained release. 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 μg/mL and 18.8 μg/mL, respectively. The target ability of FA–EPI–BSANP for SMMC 7721 cell 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.