RT Journal Article
SR Electronic
T1 Novel Liposomal Gefitinib (L-GEF) Formulations
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2919
OP 2923
VO 32
IS 7
A1 XIAOJU ZHOU
A1 BRYANT YUNG
A1 YIFEI HUANG
A1 HONG LI
A1 XIANMING HU
A1 GUANGYA XIANG
A1 ROBERT J. LEE
YR 2012
UL http://ar.iiarjournals.org/content/32/7/2919.abstract
AB Background: Gefitinib is a promising agent for the treatment of non-small cell lung cancer. The purpose of this study was to develop a novel liposomal formulation for gefitinib (L-GEF) to improve its therapeutic index. Materials and Methods: Several L-GEF formulations were prepared and characterized for their physical chemical properties and cytotoxicity. The pharmacokinetic parameters of the liposomes were determined in mice. The effect of lipid composition, transmembrane pH gradient, and incorporation of hydroxypropyl-β-cyclodextrin (HPβCD) on drug-loading efficiency, liposomal stability, and the rate of drug release were investigated. Results: The L-GEF formulation composed of hydrogenated soy phosphatidylcholine (HSPC)/cholesterol (Chol)/monomethoxy polyethylene glycol 2000-distearoyl phosphatidyl-ethanolamine (mPEG-DSPE) encapsulating 0.3 M (NH4)2SO4 and 0.1 M HPβCD (L-GEF-HSPC), had a drug-loading efficiency (DLE) of 85.5%. In vitro release studies showed that gefitinib release from L-GEF-HSPC in the presence of human plasma was slow and exhibited non-Fickian kinetics. Pharmacokinetic study in mice after i.v. bolus administration of L-GEF-HSPC showed that the area under the plasma concentration time curve (AUC) for gefitinib was 32.41 μg·h /ml and six times that of free gefitinib. The elimination half life (t1/2β) of L-GEF-HSPC was 7.29 h, while that of free gefitinib was 2.26 h. Conclusion: It was shown that gefitinib can be efficiently loaded into L-GEF-HSPC composed of HSPC/Chol/mPEG-DSPE (55/40/5 mol/mol) with 0.3 M (NH4)2SO4 and 0.1 M HPβCD as trapping agents. Compared with the free drug, L-GEF-HSPC had high drug loading, good stability, and long-circulating properties.