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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.

SUBMITTER: Guo Y

PROVIDER: S-EPMC8241045 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Guo Yang Y Zhong Ting T Duan Xiao-Chuan XC Zhang Shuang S Yao Xin X Yin Yi-Fan YF Huang Dan D Ren Wei W Zhang Qiang Q Zhang Xuan X

Drug delivery 20171101 1

In the present study, we select the Sylysia 350 (Sylysia) as mesoporous material, distearoylphosphatidylethanolamine-poly(ethylene glycol)<sub>2000</sub> (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 i ...[more]

PMID: 28165798

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Project description:The presence of active pharmaceutical ingredients (APIs) in the forms of different polymorphic states can induce differences in their physicochemical properties. In the case of poorly soluble APIs, like the oncological drug sorafenib tosylate, small variations in solubility may result in large bioavailability differences. The control of its therapeutic dose is crucial from the effective pharmacotherapy point of view and the reduction of side effects. Therefore, this study aimed to assess the influence of sorafenib tosylate polymorphic forms on its solubility and, consequently, permeability, based on passive diffusion through membranes simulating the gastrointestinal tract (GIT) conditions. In the first part of the work, two crystalline forms of sorafenib tosylate were identified using the X-ray powder diffraction, FT-IR, and Raman spectroscopy. Subsequently, solubility studies were carried out. Both forms of sorafenib tosylate were insoluble in 0.1 N hydrochloric acid (HCl), in acetate buffer (pH 4.5), and in phosphate buffer (pH 6.8). Solubility (mg/mL) of form I and III of sorafenib tosylate in 0.1 N HCl + 1.0% SDS was 0.314 ± 0.006 and 1.103 ± 0.014, respectively, in acetate buffer pH 4.5 + 1.0% SDS it was 2.404 ± 0.012 and 2.355 ± 0.009, respectively, and in phosphate buffer pH 6.8 + 1.0% SDS it was 0.051 ± 0.005 and 1.805 ± 0.023, respectively. The permeability study was assessed using the parallel artificial membrane permeability assay (PAMPA) model. The apparent permeability coefficient (Papp-cm s-1) of form I and III in pH 1.2 was 3.01 × 10-5 ± 4.14 × 10-7 and 3.15 × 10-5 ± 1.89 × 10-6, respectively, while in pH 6.8 it was 2.72 × 10-5 ± 1.56 × 10-6 and 2.81 × 10-5 ± 9.0 × 10-7, respectively. Changes in sorafenib tosylate concentrations were determined by chromatography using the high-performance liquid chromatography (HPLC)-DAD technique. As a result of the research on the structural polymorphism of sorafenib tosylate, its full spectral characteristics and the possibility of using FT-IR and Raman spectroscopy for the study of polymorphic varieties were determined for the first time, and the HPLC method was developed, which is appropriate for the assessment of sorafenib solubility in various media. The consequences of various physicochemical properties resulting from differences in the solubility of sorafenib tosylate polymorphs are important for pre-formulation and formulation studies conducted with its participation and for the safety of oncological sorafenib therapy.

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

Publications

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

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