Journal
ONCOTARGET
Volume 8, Issue 38, Pages 63311-63323Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18800
Keywords
Bufalin; bovine serum albumin; nanoparticles; hepatocellular carcinoma
Categories
Funding
- National Natural Science Foundation of China [81673739]
- Medical Research Fund of Shanghai Municipal Health and Family Planning Commission [201440365, ZY3-RCPY-3-1058]
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Objective: To prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma. Methods: Bufalin-loaded bovine serum albumin nanoparticle was prepared by desolvation method, to investigate the in vitro release performance and to evaluate the pharmacokinetic and tissue distribution. The antitumor activity against hepatocellular carcinoma was evaluated in vitro and in vivo, respectively. Results: The Bufalin-loaded bovine serum albumin nanoparticle with an average particle size of 125.1 nm exhibited a sustained release behavior in vitro. The half-life, blood plasma area under the curve and apparent volume of distribution of Bufalinloaded bovine serum albumin nanoparticle were significantly higher than that of Bufalin, whereas the clearance rate was lower than Bufalin group. The uptake of liver for Bufalin-loaded bovine serum albumin nanoparticle was 352.045 +/- 35.665 ng/g while for Bufalin was 164.465 +/- 48.080 ng/g (P < 0.01) at 5 min. The uptake of tumor for Bufalin-loaded bovine serum albumin nanoparticle was significantly higher than that of Bufalin both at 5 min (50.169 +/- 11.708 ng/g, 93.415 +/- 13.828 ng/g, P < 0.01) and 15 min (43.683 +/- 11.499 ng/g, 64.219 +/- 17.684 ng/g, P > 0.05). Bufalin-loaded bovine serum albumin nanoparticle and Bufalin have similar antitumor activity in vitro. The tumor inhibition effect of Bufalin-loaded bovine serum albumin nanoparticle was stronger than that of Bufalin alone in vivo. Conclusion: Bufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.
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