Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box-Behnken design

被引:44
|
作者
Emami, Jaber [1 ,2 ]
Rezazadeh, Mahboubeh [1 ,3 ]
Sadeghi, Hojjat [2 ,4 ]
Khadivar, Khashayar [1 ,2 ]
机构
[1] Isfahan Univ Med Sci, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut, Esfahan, Iran
[2] Isfahan Univ Med Sci, Sch Pharm & Pharmaceut Sci, Isfahan Pharmaceut Sci Res Ctr, Esfahan, Iran
[3] Isfahan Univ Med Sci, Sch Pharm & Pharmaceut Sci, Novel Drug Delivery Syst Res Ctr, Esfahan, Iran
[4] Isfahan Univ Med Sci, Pharm & Pharmaceut Sci, Dept Med Chem, Esfahan, Iran
关键词
BBB; cancer; NLC; PTX; IN-VIVO EVALUATION; TARGETED DRUG-DELIVERY; PLGA NANOPARTICLES; ANTITUMOR-ACTIVITY; CONTROLLED-RELEASE; VITRO; BARRIER; GLIOBLASTOMA; CYTOTOXICITY; FORMULATION;
D O I
10.1080/10837450.2016.1189933
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The treatment of brain cancer remains one of the most difficult challenges in oncology. The purpose of this study was to develop transferrin-conjugated nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX). PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the impact of various formulation variables were assessed using Box-Behnken design. Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro cytotoxicity of it was investigated against U-87 brain cancer cell line. As a result, 14.1mg of cholesterol, 18.5mg of triolein, and 0.5% poloxamer were used to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted formulation were confirmed to be 205.4 +/- 11 nm, 25.7 +/- 6.22mV, 91.8 +/- 0.5%, 5.38 +/- 0.03% and 29.3 h, respectively. Following conjugation of optimized PTX-NLCs with transferrin, coupling efficiency was 21.3mg transferrin per mmol of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non-significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could potentially be exploited as a delivery system in brain cancer cells.
引用
收藏
页码:370 / 382
页数:13
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