Bufalin-loaded bovine serum albumin nanoparticles demonstrated improved anti-tumor activity against hepatocellular carcinoma: preparation, characterization, pharmacokinetics and tissue distribution

Abstract

ObjectiveTo prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.MethodsBufalin-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.ResultsThe 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 Bufalin-loaded 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.ConclusionBufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.

Encapsulation of epigallocatechin-3-gallate into albumin nanoparticles improves pharmacokinetic and bioavailability in rat model

“…the administration showed a significant increase in AUC and T 1/2 when compared with the free drug (Desale et al 2018). Studies on curcumin loaded albumin nanoparticles and bufalin loaded albumin nanoparticles also showed similar results (Jithan et al 2011;Zhang et al 2017). In the present study, Alb-NP-EGCG also showed an increase in plasma concentration, AUC, higher retention time when compared with the free EGCG.…”

“…Similarly, studies on albumin nanoparticles loaded with docetaxel also showed a minimal hepatoxicity when compared with the free drug (Desale et al 2018). Other drugs loaded into albumin nanoparticles were also found to be safe and effective (Zhang et al 2017;Casa et al 2018).…”

Determination of Endogenous Bufalin in Serum of Patients With Hepatocellular Carcinoma Based on HPLC-MS/MS

“…In the early stage of the research group, HPLC-MS/MS was established to determine the concentration of bufalin in rats after intravenous administration. The methodological results of the determination of each biological sample show that the linearity, precision, and accuracy of the method are satisfactory (29). In this study, for the first time HPLC-MS/MS was used to qualitatively and quantitatively analyze and examine the differences of endogenous bufalin from HCC patients and healthy volunteers in serum.…”

Anticancer and Immunogenic Properties of Cardiac Glycosides

“…The tumor inhibition effect of bufalin-loaded BSA nanoparticles was stronger than that of bufalin alone in vivo. In this way, bufalin-loaded BSA nanoparticles seem to be a promising liver-targeted drug delivery system with a high liver uptake and a strong antitumor activity against hepatocellular carcinoma [ 94 ].…”