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

Title
Modulation of Pharmacokinetic and Cytotoxicity Profile of Imatinib Base by Employing Optimized Nanostructured Lipid Carriers
Author
최한곤
Keywords
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
Issue Date
2015-09
Publisher
SPRINGER/PLENUM PUBLISHERS
Citation
PHARMACEUTICAL RESEARCH, v. 32, No. 9, Page. 2912-2927
Abstract
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.
URI
https://link.springer.com/article/10.1007/s11095-015-1673-7http://hdl.handle.net/20.500.11754/39276
ISSN
0724-8741; 1573-904X
DOI
10.1007/s11095-015-1673-7
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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