Title:A New Antitumor Agent, (3-chloro-7-methoxyfuro[2,3-b]-quinolin-4-yl)-(4-methoxyphenyl) amine, Loaded in Solid Lipid Nanoparticles: Characterization and Pharmacokinetics
Volume: 8
Issue: 2
Author(s): Yi-Ping Fang, Pao-Chu Wu, Cherng-Chyi Tzeng, Yeh-Long Chen, Huei-Lan Lin and Yi-Hung Tsai
Affiliation:
Keywords:
(3-chloro-7-methoxyfuro[2, 3-b]-quinolin-4-yl)-(4-methoxyphenyl)amine (CYL), biodistribution, glyceryl monostearate, highperformance
liquid chromatography, pharmacokinetics, solid lipid nanoparticles (SLNs)
Abstract: (3-Chloro-7-methoxyfuro[2,3-b]-quinolin-4-yl)-(4-methoxyphenyl)amine (CYL), a chemotherapeutic agent, is an analogue of
amsacrine. The water insolubility of CYL limits its delivery and thus its application. The aim of the study was to utilize solid lipid
nanoparticles (SLNs) to improve the delivery of CYL, and investigate its biodistribution behavior in an animal model. Characterizations
of SLNs were evaluated including the particle size, zeta potential and entrapment efficiency. An in vivo study was used to investigate the
pharmacokinetics and biodistribution behaviors. We established a rapid and sensitive high-performance liquid chromatographic (HPLC)
technique with electrochemical detection to determine CYL, and the limit of detection was 40 ng/ml. We found that particle sizes of
CYL-loaded SLNs were about 25%~33% larger then empty SLNs. The entrapment efficiency (E%) of CYL embedded in the SLN matrix
was about 80%~98%. Moreover, the E% of SLNs incorporating glyceryl monostearate (GMS) significantly increased by about
11%~17% and the polydispersity index dropped 0.3~0.39. An in vivo pharmacokinetics study of intravenous CYL displayed linear
plasma pharmacokinetics and fit a two-compartment model. The biodistribution behavior demonstrated that CYL-loaded tristearin(TS)-
GMS SLNs mainly accumulated in the heart, lungs, liver, pancreas, and kidneys.
