Deoxycholic Acid Modified-carboxymethyl Curdlan Conjugate As a Novel Carrier of Epirubicin: in Vitro and in Vivo Studies

Deoxycholic acid hydrophobically modified-carboxymethylated-curdlan (DCMC) conjugate was developed as a novel carrier for the anticancer drugs. Epirubicin (EPB), as a model drug, was physically loaded into DCMC self-assembled nanoparticles. EPB-loaded DCMC nanoparticles were almost spherical in shape and their size, in the range of 327.4-511.5 nm, increased with the EPB-loading content increasing. In vitro release of EPB from DCMC self-assembled nanoparticles showed sustained drug release pattern and the release rate was related to pH of release media and drug loading content. The cytotoxic activity of EPB-loaded DCMC nanoparticles was assayed by the MTT colorimetric assay. Compared with free drug, EPB-loaded DCMC nanoparticles showed the higher cytotoxicity, which may be attributed to the enhanced cellular uptake. In vivo toxicity study indicated that DCMC conjugate did not induce unexpected side effects. Tissue biodistribution study was performed in tumor-bearing mice. The result showed that DCMC increased the uptake of EPB in the tumor and decreased the uptake of EPB in kidney and heart, compared to free drug. Moreover, tumor volume reductions induced by DCMC conjugate, free EPB and EDNs were 24.3%, 58.9% and 70%, respectively, which suggested that EDNs could effectively retard the growth of the tumor.