Modulation of Pharmacokinetic and Cytotoxicity Profile of Imatinib Base by Employing Optimized Nanostructured Lipid Carriers

被引:38
作者
Gupta, Biki [1 ]
Poudel, Bijay Kumar [1 ]
Tuan Hiep Tran [1 ]
Pradhan, Roshan [1 ]
Cho, Hyuk-Jun [1 ]
Jeong, Jee-Heon [1 ]
Shin, Beom Soo [2 ]
Choi, Han-Gon [3 ]
Yong, Chul Soon [1 ]
Kim, Jong Oh [1 ]
机构
[1] Yeungnam Univ, Coll Pharm, Kyongsan 712749, South Korea
[2] Catholic Univ Daegu, Coll Pharm, Gyongsan 712702, South Korea
[3] Hanyang Univ, Inst Pharmaceut Sci & Technol, Coll Pharm, Ansan 426791, South Korea
关键词
nanostructured lipid carrier; imatinib base; Plackett-Burman design; central composite design; bioavailability; RESPONSE-SURFACE METHODOLOGY; RESISTANT CANCER-CELLS; DRUG-DELIVERY SYSTEM; IN-VIVO; DESIGN; NANOPARTICLES;
D O I
10.1007/s11095-015-1673-7
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To prepare, optimize and characterize imatinib-loaded nanostructured lipid carriers (IMT-NLC), and evaluate their pharmacokinetic and cytotoxicity characteristics. IMT-NLC was prepared by hot homogenization method, and optimized by an approach involving Plackett-Burman design (PBD) and central composite design (CCD). An in vivo pharmacokinetic study was conducted in rats after both oral and intravenous administration. The in vitro cytotoxicity was evaluated by MTT assay on NCI-H727 cell-lines. PBD screening, followed by optimization by CCD and desirability function, yielded an optimized condition of 0.054, 6% w/w, 2.5% w/w and 1.25% w/v for organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), amount of lecithin (Lec) and amount of TweenA (R) 20 (Tw20) respectively. The optimized IMT-NLC exhibited a particle size (S-z) of 148.80 A +/- 1.37 nm, polydispersity index (PDI) 0.191 A +/- 0.017 of and zeta-potential of -23.0 A +/- 1.5 mV, with a drug loading (DL) of 5.48 A +/- 0.01% and encapsulation efficiency (EE) of 97.93 A +/- 0.03%. IMT-NLC displayed sustained IMT release in vitro, significantly enhanced in vivo bioavailability of IMT after intravenous and oral administration, and greater in vitro cytotoxicity on NCI-H727 cells, compared with free IMT. A combined DoE approach enabled accurate optimization and successful preparation of IMT-NLC with enhanced in vivo pharmacokinetic and in vitro cytotoxicity characteristics.
引用
收藏
页码:2912 / 2927
页数:16
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