Evaluation of Docetaxel-Loaded Intravenous Lipid Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Activity, Safety and Toxicity

Zhao, Mingming; Su, Min; Xia, Lin; Luo, Yanfei; He, Huan; Cai, Cuifang; Tang, Xing

doi:10.1007/s11095-010-0180-0

Cited by 54 publications

(25 citation statements)

References 26 publications

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“…As in the case of AUC, plasma clearance (CL p ) and volume of distribution (V d ), rats following liposomes administration were characterised by markedly higher AUCs (97.2%, **p50.01), slower CL p (49.2%, **p50.01) and lower V d (42.5%, **p50.01). It was in accordance with previous findings, where lipophilic drugs given in lipid carriers showed higher plasma concentration following intravenous injection than solution forms (Shi et al, 2009;Zhao et al, 2010).…”

Section: Pk Study Of Ltx Solution and Modified Liposomessupporting

confidence: 93%

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes

Zhou

Zhang

et al. 2016

Xenobiotica

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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.

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Section: Pk Study Of Ltx Solution and Modified Liposomessupporting

confidence: 93%

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes

Zhou

Zhang

et al. 2016

Xenobiotica

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“…5 Taxanes including paclitaxel (Taxol™) and docetaxel (DTX; Taxotere™) are remarkable cytotoxic compounds and are the representative chemotherapeutic anticancer drugs that are clinically well established. 6 DTX, as well as paclitaxel, binds to microtubules and consequently stabilizes microtubules by enhancing the rates of nucleation, growth, and elongation phases of polymerization, leading to mitotic arrest, inhibition of cell proliferation, and stimulation of cell death. 7 Taxanes are largely insoluble in water.…”

mentioning

confidence: 99%

Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Choi¹,

Ko²,

Chung³

et al. 2015

IJN

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Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO 2 ), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs.

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“…Lipid emulsions were prepared using a high pressure homogenization system (Nanomizer, Yoshida Kikai Co., Ltd., Nagoya, Japan) as previously described (Zhao et al, 2010). In brief, purified phospholipids (DCP or SA) and coumarin-6 were dissolved in MCT with gentle heating.…”

Section: Preparation Of Coumarin-6 Loaded Lipid Emulsionsmentioning

confidence: 99%

Drug delivery to the ocular posterior segment using lipid emulsion via eye drop administration: Effect of emulsion formulations and surface modification

Lin

Tahara

Takeuchi

2013

International Journal of Pharmaceutics

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Evaluation of Docetaxel-Loaded Intravenous Lipid Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Activity, Safety and Toxicity

Abstract: The DLE investigated in this paper was found to be an attractive new formulation and an appropriate choice for the clinical administration of docetaxel.

Cited by 54 publications

References 26 publications

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes

Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Drug delivery to the ocular posterior segment using lipid emulsion via eye drop administration: Effect of emulsion formulations and surface modification

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