Modulation of Pharmacokinetic and Cytotoxicity Profile of Imatinib Base by Employing Optimized Nanostructured Lipid Carriers.
OBJECTIVE
To prepare, optimize and characterize imatinib-loaded nanostructured lipid carriers (IMT-NLC), and evaluate their pharmacokinetic and cytotoxicity characteristics.


METHODS
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.


RESULTS
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 Tween® 20 (Tw20) respectively. The optimized IMT-NLC exhibited a particle size (Sz) of 148.80 ± 1.37 nm, polydispersity index (PDI) 0.191 ± 0.017 of and ζ-potential of -23.0 ± 1.5 mV, with a drug loading (DL) of 5.48 ± 0.01% and encapsulation efficiency (EE) of 97.93 ± 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.


CONCLUSIONS
A combined DoE approach enabled accurate optimization and successful preparation of IMT-NLC with enhanced in vivo pharmacokinetic and in vitro cytotoxicity characteristics.
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
Biki
B
Gupta
Bijay Kumar
BK
Poudel
Tuan Hiep
TH
Tran
Roshan
R
Pradhan
Hyuk-Jun
HJ
Cho
Jee-Heon
JH
Jeong
Beom Soo
BS
Shin
Han-Gon
HG
Choi
Chul Soon
CS
Yong
Jong Oh
JO
Kim
D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D000068877:Imatinib Mesylate / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D054709:Lecithins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D054709:Lecithins; D008055:Lipids; D011136:Polysorbates; D000068877:Imatinib Mesylate