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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

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(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.
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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)

Document Type: Research Article

Publication date: 2012-04-01

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