Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes. (4th May 2017)

• Record Type: Journal Article
• Authors: Lu, Xue-Feng; Zhou, Yang; Zhang, Jian; Wang, Guo-Qin
• Is Part Of: Xenobiotica. Volume 47:Number 5(2017)
• Page Start: 416
• Page End: 422
• Publication Date: 2017-05-04
• Subjects: Folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) -- larotaxel -- liposomes -- pharmacokinetics -- tissue distribution; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2016.1195936
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 1. The aim of this study was to compare the pharmacokinetics (PKs) and tissue distribution of larotaxel (LTX) solution with a newly developed formulation called LTX-loaded folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL)-modified liposomes in rats. 2. An ultra-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the determination of LTX in rat plasma and tissues to investigate the influence of FA-PEG-PCHL-modified lipid carrier on LTX PKs and tissue distribution. 3. The PK study result showed significantly higher area under the concentration-time curve (97.2%, ** p < 0.01), slower clearance (49.2%, ** p < 0.01) and lower volume of distribution (42.5%, ** p < 0.01) in rats following intravenous administration of modified liposomes. The biodistribution results exhibited significantly lower uptake of LTX-loaded modified liposomes in heart (20.4%, ** p < 0.01), lung (8.33%, ** p < 0.01), muscle (13.4%, * p < 0.05) and spleen (15.0%, ** p < 0.01) among all sampled tissues, indicating that the modified lipid carriers may avoid the trapping by the reticuloendothelial system and the modified liposomes may reduce toxicity in cardiovascular system compared to LTX solution. Moreover, markedly higher concentrations of LTX in the kidney (100%, ** p < 0.01) were found in LTX-loaded modified liposome treated rats and could be explained by the high folate receptor level in kidney. 4. These results indicated that the FA-PEG-PCHL-modified liposome could be an effective parenteral carrier for the delivery of LTX in cancer treatment.