Improving anti-tumor activity of sorafenib tosylate by lipid- and polymer-coated nanomatrix.
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.
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Yang
Y
Guo
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Ting
T
Zhong
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Xiao-Chuan
XC
Duan
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Shuang
S
Zhang
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Xin
X
Yao
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Yi-Fan
YF
Yin
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Dan
D
Huang
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Wei
W
Ren
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.|c State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing , China.
Qiang
Q
Zhang
a Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing , China.|b Department of Pharmaceutics , School of Pharmaceutical Sciences, Peking University , Beijing , China , and.
Xuan
X
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007785:Lactose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077157:Sorafenib; D047368:Tumor Burden / Q000187:drug effects* / Q000502:physiology
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D010714:Phosphatidylethanolamines; D011108:Polymers; C509290:hydroxypropylmethylcellulose-lactose matrix; D009536:Niacinamide; D011092:Polyethylene Glycols; D008747:Methylcellulose; D000077157:Sorafenib; D007785:Lactose
Sorafenib tosylate; anti-tumor activity; bioavailability; nanomatrix; poorly water-soluble drugs