Improving anti-tumor activity of sorafenib tosylate by lipid- and polymer-coated nanomatrix

Abstract

In the present study, we select the Sylysia 350 (Sylysia) as mesoporous material, distearoylphosphatidylethanolamine-poly(ethylene glycol) 2000 (DSPE-PEG) as absorption enhancer and hydroxy propyl methyl cellulose (HPMC) as crystallization inhibitor to prepare sorafenib tosylate (SFN) nanomitrix (MSNM@SFN) for improving the anti-tumor activity of SFN. The MSNM@SFN was prepared by solvent evaporation method. The solubility, dissolution, and bioavailability of SFN in MSNM@SFN were also investigated. The anti-tumor activity of MSNM@SFN was evaluated in vitro and in vivo. Our results indicated that the solubility and dissolution of SFN in MSNM@SFN were significantly increased. The oral bioavailability of SFN in MSNM@SFN was greatly improved 7.7-fold compared with that in SFN suspension. The enhanced anti-tumor activity of MSNM@SFN was confirmed in vitro and in vivo experiments. This nanomatrix developed in this study could be a promising drug delivery platform for improving the therapeutic efficacy of poorly water-soluble drugs.

<p>Enhancing Anti-Tumor Activity of Sorafenib Mesoporous Silica Nanomatrix in Metastatic Breast Tumor and Hepatocellular Carcinoma via the Co-Administration with Flufenamic Acid</p>

“…In our previous research, we prepared SFN mesoporous silica nanomatrix (MSNM@SFN) to improve the solubility, dissolution, and bioavailability of SFN. 26 The enhanced anti-tumor activity of MSNM@SFN compared with SFN suspension was confirmed in MDA-MB-231 cells in vitro and in vivo. 26 Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti-inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN.…”

“…We prepared SFN mesoporous silica nanomatrix (MSNM@SFN) at the ratio that SFN:Sylysia:HPMC: DSPE-PEG was 1:3:3:3 (w/w/w/w) as our previous research. 26 For preparation of MSNM@SFN+FFA, the MSNM@SFN was mixed with FFA at the ratio of MSNM@SFN:FFA 40:1 (w/w) or SFN:FFA 4:1(w/w). The dose of MSNM@SFN was 40 mg/kg of SFN similar with that in MDA-MB-231 tumor-bearing nude mice model.…”

The theranostic efficiency of tumor-specific, pH-responsive, peptide-modified, liposome-containing paclitaxel and superparamagnetic iron oxide nanoparticles

“…The in vitro antitumor activity of PTX/SPIO-SSL-H 7 K(R 2 ) 2 was evaluated in MDA-MB-231 cell line following our previously reported method. 23,24,[28][29][30][31] Briefly, MDA-MB-231 cells (1×10 4 cells/well) were seeded in 96-well plates and incubated for 24 h. Then, the cells were treated with cell culture medium (pH 6.8 or pH 7.4) containing different amounts of PTXloaded liposomes and incubated for 48 h at 37°C. The cell viability was determined by sulforhodamine B assay.…”

“…Zheng et al subcutaneous injection of 0.2 mL MDA-MB-231 cell suspension (5×10 6 cells) with 20% basement membrane matrix into the right leg of each female BALB/c nude mouse. 31 Once the tumor masses reached ~200-300 mm 3 in volume, the mice were randomly assigned to four groups (six animals per group): group I was given a 5% glucose solution, group II was given PTX-SSL (15 mg/kg, i.v., twice a day for 4 days [q4d]), group III was given PTX/SPIO-SSL (15 mg/kg, i.v., q4d), and group IV was given PTX/SPIO-SSL-H 7 K(R 2 ) 2 (15 mg/kg, i.v., q4d). For all administrations, the formulations were given via the tail vein.…”

Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo

“…The in vitro cytotoxicity of NPPA-PTX@PEG NPs was measured using SRB. 17 MDA-MB-231 cells (1×10 4 cells/well) were seeded in 96-well plates, incubated for 24 hours, and then treated with NPPA-PTX@PEG NPs at 37°C for 48 hours. The cell viability was determined using SRB, which allowed quantification of the living cells by measuring absorbance at 540 nm by a 96-well plate reader (model 680; Bio-Rad Laboratories Inc., Hercules, CA, USA).…”