Development of a validated LC–APCI-MS/MS method to study the plasma and tumor distribution of CHO-PTX intravenous lipid emulsion

Xia, Xuejun; Song, Xiaowei; Xu, Jiaming; He, Jiuming; Peng, Jie; Zhang, Xiang; Jin, Dujia; Abliz, Zeper; Liu, Yuling

doi:10.1016/j.jpba.2015.05.023

Cited by 2 publications

(3 citation statements)

References 38 publications

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“…Previous efforts on improving its stability have been focused on developing the paclitaxel-cholesterol prodrug with increased lipophilicity (20,21). What we found is that the lipid emulsion loaded with the paclitaxel-cholesterol prodrug Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors exhibited long-term stability and high intratumoral accumulation (20), but the in vivo antitumor effect was greatly reduced in comparision to Taxol (unpublished data), which may attribute to the low concentration of PTX released from the paclitaxel-cholesterol prodrug by in vivo enzymatic cleavage. Alternatively, a paclitaxel-cholesterol complex connected by intermolecular hydrogen bonds was prepared and a novel lipid emulsion (PTX-CH Emul), which was composed of a paclitaxel-cholesterol complex surrounded by a phospholipid monolayer, was engineered in our previous study (22).…”

Section: Introductionmentioning

confidence: 99%

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors

Liu

Xia

et al. 2016

Oncology Reports

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The aim of the present study was to develop a lipid emulsion loaded with a paclitaxel-cholesterol complex (PTX-CH Emul) in order to improve the safety and efficacy of paclitaxel (PTX) and evaluate its antitumor activity against commercially available formulation Taxol®. PTX-CH Emul resembling a low density lipoprotein lipid structure, exhibited an ideal particle size, high drug loading capability, high drug encapsulation efficiency and excellent stability. PTX-CH Emul showed superior in vitro anticancer efficacy against triple-negative MDA-MB-231 breast cancer cells when compared with a paclitaxel emulsion (PTX Emul) and Taxol. The IC70 value of PTX-CH Emul was almost 1.5- and 2.4-fold lower than that of PTX Emul and Taxol, respectively. Compared with PTX Emul and Taxol, PTX-CH Emul exhibited stronger and more rapid inhibitory effects on 3D tumor spheroids of MDA-MB-231 cells. Additionally, in vivo tumor-targeting study showed that PTX-CH Emul had higher specificity and efficiency in intratumoral accumulation as compared to PTX Emul. Finally, the maximum tolerated dose (MTD) of PTX-CH Emul was 2.25‑fold higher than that of Taxol, suggesting that PTX-CH Emul exhibited better safety profiles in vivo than Taxol. At the MTDs, PTX-CH Emul exhibited superior antitumor efficacy in nude mice bearing MDA-MB-231 xenografts in comparison to Taxol. Therefore, PTX-CH Emul as reported here showed high potential as a drug carrier for PTX in clinical applications involving the targeting of triple-negative breast cancer.

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Section: Introductionmentioning

confidence: 99%

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors

Liu

Xia

et al. 2016

Oncology Reports

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“…, ; Xia et al . , ). Despite the advantages offered by our current method with respect to sample handling and pre‐analytical processing, further improvements are required with respect to the limit of detection (sensitivity) and analysis time (retention).…”

Section: Resultsmentioning

confidence: 97%

“…, ; Xia et al . , ). In particular, liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) is a well‐established analytical tool owing to its inherent specificity and sensitivity.…”

Section: Introductionmentioning

confidence: 97%

Development and qualification of an LC–MS/MS method for investigating the biological implications of micelle entrapped paclitaxel in cell culture and rats

Kaddoumi

Gill

Elfakhri

et al. 2017

Biomedical Chromatography

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Paclitaxel is a front-line antineoplastic drug used in chemotherapeutic modalities for treatment of various types of malignancies. However, its efficacy is limited by dose-related toxicities. In this study, we have explored two important biological aspects of entrapping paclitaxel in PEG -DSPE micelles. First, we evaluated the impact of this micellar delivery system on P-glycoprotein (P-gp)-paclitaxel interaction, and we investigated differences in plasma pharmacokinetics of free and micelle-entrapped paclitaxel. For quantification of paclitaxel, an LC-MS/MS method was developed. Paclitaxel was extracted from samples using a simple one-step protein precipitation. Chromatographic conditions included a C column with a mobile phase consisting of 0.1% formic acid in acetonitrile-water (60:40, v/v) pumped at 1 mL/min. The lower limit of quantitation in both plasma and cell lysate was 1.0 ng/mL. The quantitative linear range was 1-1000 ng/mL. In addition, P-gp efflux studies on free and micellar paclitaxel showed the proficiency of PEG -DSPE micelles in evading P-gp-mediated efflux, thus increasing paclitaxel uptake. Furthermore, the micellar paclitaxel levels were maintained in the body for longer time as compared with taxol, which is desirable for increasing the efficacy of paclitaxel in cancer treatment.

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Development of a validated LC–APCI-MS/MS method to study the plasma and tumor distribution of CHO-PTX intravenous lipid emulsion

Cited by 2 publications

References 38 publications

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors

Development and qualification of an LC–MS/MS method for investigating the biological implications of micelle entrapped paclitaxel in cell culture and rats

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