Journal
NANO
Volume 8, Issue 6, Pages -Publisher
WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S1793292013500665
Keywords
Epirubicin hydrochloride; bovine serum album; folate; target delivery; nanoparticles; adsorption; desolvation; targeted drug delivery
Funding
- Fundamental Research Funds for the Central Universities [DL12EA01-02]
- National Natural Science Foundation of China [21203018]
- Agricultural Science and Technology Achievements Transformation Fund Programs of the Ministry of Science and Technology [2011GB23600016]
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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 mu g/mL and 18.8 mu g/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.
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