Improved Oral Bioavailability and Liver Targeting of Sorafenib Solid Lipid Nanoparticles in Rats

被引:0
作者
Haipeng Wang
Huiyun Wang
Wenlong Yang
Mengjie Yu
Shuilin Sun
Baogang Xie
机构
[1] Nanchang University,Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science
来源
AAPS PharmSciTech | 2018年 / 19卷
关键词
sorafenib; solid lipid nanoparticle; evaluation; liver targeting; pharmacokinetics;
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摘要
Minimal information is available on the oral bioavailability and liver-targeting properties of sorafenib solid lipid nanoparticles (SRF-SLNs) in rats. In this study, SRF-SLNs were prepared via the combined methods of high-speed shearing and ultrasonic treatment. SRF-SLN formulations were also optimized. Particle size, zeta potential, entrapment efficiency (EE), and drug loading (DL) were used as indices for the evaluation of the as-prepared SRF-SLNs. SRF concentration was determined by the high-performance liquid chromatography method. Results showed that the average EE and DL of SRF-SLNs were 89.87 and 5.39%. The average particle size, polydispersity index, and zeta potential of SRF-SLNs were 77.16 nm, 0.28, and − 18.1 mV, respectively. The results of the stability test showed that SRF-SLNs remained stable for more than 1 month at room temperature. After oral administration to rats (7.5 mg/kg), the liver-targeting evaluation results showed that the average drug selectivity index value of SRF-SLNs was 2.20 times higher, than that of the SRF-suspension. Furthermore, the area under the concentration–time curve of SRF increased by 66.7% in the SRF-SLN group comparing with that in the SRF-suspension. Our results suggested that SLNs were a promising approach for the oral delivery of SRF.
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页码:761 / 768
页数:7
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  • [1] Tang K(2011)Advance in the research of sorafenib, a multiple targeted antitutor agent Chin New Drugs J 20 2434-2441
  • [2] Li Y(2007)Sorafenib in advanced clear-cell renal-cell carcinoma N Engl J Med 356 125-134
  • [3] Chen XG(2007)Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors Oncologist 12 426-437
  • [4] Escudier B(2016)Improving Oral Bioavailability of sorafenib by optimizing the “Spring” and “Parachute” based on molecular interaction mechanisms Mol Pharm 13 599-608
  • [5] Eisen T(2012)A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a Children’s Oncology Group Phase I Consortium report Clin Cancer Res 18 6011-6022
  • [6] Stadler WM(2011)Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and nanomatrix for oral administration to rat Int J Pharm 419 339-346
  • [7] Szczylik C(2014)The use of lipid-coated nanodiamond to improve bioavailability and efficacy of sorafenib in resisting metastasis of gastric cancer Biomaterials 35 4565-4572
  • [8] Oudard S(2017)Improving anti-tumor activity of sorafenib tosylate by lipid- and polymer-coated nanomatrix Drug Deliv 24 270-277
  • [9] Siebels M(2008)Cyclosporine-loaded solid lipid nanoparticles (SLN): drug-lipid physicochemical interactions and characterization of drug incorporation Eur J Pharm Biopharm 68 535-544
  • [10] Negrier S(2004)Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs J Pharm Pharmacol 56 1527-1535