Antitumor activity of sorafenib-incorporated nanoparticles of dextran/poly(dl-lactide-co-glycolide) block copolymer

Abstract

Sorafenib-incoporated nanoparticles were prepared using a block copolymer that is composed of dextran and poly(DL-lactide-co-glycolide) [DexbLG] for antitumor drug delivery. Sorafenib-incorporated nanoparticles were prepared by a nanoprecipitation-dialysis method. Sorafenib-incorporated DexbLG nanoparticles were uniformly distributed in an aqueous solution regardless of the content of sorafenib. Transmission electron microscopy of the sorafenib-incorporated DexbLG nanoparticles revealed a spherical shape with a diameter < 300 nm. Sorafenib-incorporated DexbLG nanoparticles at a polymer/drug weight ratio of 40:5 showed a relatively uniform size and morphology. Higher initial drug feeding was associated with increased drug content in nanoparticles and in nanoparticle size. A drug release study revealed a decreased drug release rate with increasing drug content. In an in vitro anti-proliferation assay using human cholangiocarcinoma cells, sorafenib-incorporated DexbLG nanoparticles showed a similar antitumor activity as sorafenib. Sorafenib-incorporated DexbLG nanoparticles are promising candidates as vehicles for antitumor drug targeting.

Figure 1

Chemical structure of sorafenib (a) and DexbLG copolymer (b).

Figure 2

TEM images of sorafenib-incorporated nanoparticles. Polymer:drug empty nanoparticle (a), 40:2 (b), 40:5 (c), 40:7 (d) nanoparticles.

Figure 3

1H NMR spectra. Sorafenib in DMSO (a); SORA-NP, sorafenib-incorporated nanoparticles in DMSO (b); and SORA-NP in D₂O (c). The box shows typical peaks of sorafenib (a), and the arrow shows typical peaks of PLGA (b).

Figure 4

Sorafenib release from the DexbLG nanoparticles. Time course of the absolute amount of released sorafenib (a) and total percentage of released sorafenib from DexbLG nanoparticles (b). Drug release experiment of 40:2 (filled circle), 40:5 (empty circle), and 40:7 (inverted filled triangle) was performed with PBST, and 40:5 (PBS; empty triangle) was performed with PBS only.

Figure 5

Growth inhibition of HuCC-T1 cells by treatment of sorafenib-incorporated DexbLG nanoparticles. Two thousand cells were exposed to sorafenib, empty nanoparticles, and sorafenib-incorporated nanoparticles for 48 h.