In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions

Zhao, Yongxing; Liu, Dan-Xing; Liang, Wenquan; Ye, Zhiwei

doi:10.1111/j.2042-7158.2012.01484.x

Cited by 10 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, it had been reported that positively charged nanorods were selectively accumulated in angiogenic endothelial cells of tumor; the ζ potential of HCPT NRs was 24.2 ± 0.7 mV, which may explain the high distribution of nanorods in tumor further. 44,45…”

Section: Resultsmentioning

confidence: 99%

Hydroxycamptothecin Nanorods Prepared by Fluorescently Labeled Oligoethylene Glycols (OEG) Codendrimer: Antitumor Efficacy in Vitro and in Vivo

et al. 2016

View full text Add to dashboard Cite

Nanorods based on dendrimers were explored as excellent candidates for nanoscale drug delivery system. In this study, fluorescently labeled PAMAM-b-oligoethylene glycols codendrimer (POC) was utilized as carrier to prepare 10-hydroxycamptothecin (HCPT) loaded nanorods (HCPT NRs) via antisolvent precipitation method augmented by ultrasonication with the optimized drug-loading content (∼90.6%) and positive charged surface. The nanorods presented high stability, and the release of HCPT nanorods showed a sustained release manner and was completed within 48 h. The nanorods presented higher cytotoxicity against HepG2 and 4T1 cells than HCPT injections, and the cellular uptake mechanism was proved to involve clathrin-mediated endocytosis and macropincytosis-dependent endobytosis. Importantly, the HCPT nanorods resulted in strong antitumor efficacy on the H22 liver tumor model, and no significant adverse effects was observed. Besides, in vivo studies also showed that HCPT NRs possessed better tumor accumulation over HCPT injection at the equivalent concentration. According to the high drug-loading content, enhanced antitumor efficacy, and appropriate particle size, HCPT NRs as the safe and efficient drug delivery systems could have potential application for cancer chemotherapy in clinic.

show abstract

Section: Resultsmentioning

confidence: 99%

Hydroxycamptothecin Nanorods Prepared by Fluorescently Labeled Oligoethylene Glycols (OEG) Codendrimer: Antitumor Efficacy in Vitro and in Vivo

et al. 2016

View full text Add to dashboard Cite

show abstract

“…H22 cells were removed from the abdominal cavity of a mouse within 9 to 11 d after inoculation. 8) In the experiment to assess the anti-tumour effect of HDE, H22 cells (1 × 10 6 ) were prepared by Hank's balanced salt solution and inoculated subcutaneously (0.1 mL) into the left axillary region of each mouse. When the tumour size reached to 4 to 6 mm, the experiment was initiated.…”

Section: Methodsmentioning

confidence: 99%

Anti-tumour Effect and Pharmacokinetics of an Active Ingredient Isolated from <i>Inonotus hispidus</i>

Yang

Bao

Wang

et al. 2019

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Inonotus hispidus is an anti-tumour drug used in folk medicine. (4S,5S)-4-Hydroxy-3,5-dimethoxycyclohex-2-enone (HDE) is a compound isolated from Inonotus hispidus for the first time. However, the mechanisms underlying its therapeutic effects have not been elucidated. In this study, the in vitro screening, in vivo anti-tumour effects, mechanism of action, pharmacokinetics, and tissue distribution of HDE were investigated. HDE could inhibit the proliferation of HepG2 cells. Additionally, its half-maximal inhibitory concentration was 7.9 µg/mL. Increasing HDE concentrations significantly increased apoptosis rate in a dose-dependent manner. Furthermore, HDE was rapidly absorbed into mouse plasma, reaching a maximum concentration at 30 min. The area under the plasma HDE concentration-time curves for the studied organs were as follows: spleen > liver > lung > kidney > muscle > thymus > heart > brain. HDE also inhibited tumour growth up to 69%. The weights of organs harvested from HDE-treated mice were not significantly different from those harvested from control mice. Furthermore, HDE upregulated Fas expression and downregulated FasL expression in HepG2 cells. HDE significantly increased caspase-3 and caspase-8 activity. The antitumour effect of HDE might be realized by activating the Fas-mediated apoptotic pathway. We also found that HDE undergoes enterohepatic circulation or is quickly absorbed by the body, and the drug is released back into systemic circulation. In conclusion, HDE significantly inhibited H22 hepatocarcinoma cells (H22) tumour growth in mice without damaging organs; therefore, it may be suitable for treating liver cancer.

show abstract

“…This was mainly due to the quick transport of 10-HCPT nanocrystals from the blood to organs such as the liver and spleen upon entering the circulatory system, which has been extensively reported. 21,30 The results presented in Table 3 showed that there were significant differences in the pharmacokinetic parameters between nanocrystals and injections groups. The elimination half-life of the 10-HCPT nanocrystals group was 2.98-fold as high as that of the injections group (P,0.001), and the area under the curve within 24 hours (AUC 0-24 ) value was 2.81-fold as high as the injections group.…”

mentioning

confidence: 97%

A stabilizer-free and organic solvent-free method to prepare 10-hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation

Yang¹,

Liu²,

Zhao³

et al. 2016

IJN

View full text Add to dashboard Cite

10-Hydroxycamptothecin (10-HCPT) is a promising anticancer drug with a wide spectrum of antitumor activities. Due to its poor solubility, the carboxylate form that shows high water solubility but minimal anticancer activity and pharmacokinetic defects is used in the marketed 10-HCPT injections, resulting in its limited clinical application. To develop a simple, safe, and highly effective drug delivery system, a modified acid–base microprecipitation combined with a high-pressure homogenization technique was adopted to prepare 10-HCPT nanocrystals. Neither organic solvents nor stabilizers were employed throughout the preparation process. The in vitro and in vivo performances of the resulting10-HCPT nanocrystals were investigated systematically. The nanocrystals were spherical with a small size of ~130 nm, and the actual drug-loading content was as high as 75%. The nanocrystals displayed a sustained release pattern and were proven to have a higher cell uptake and antiproliferative activity than the 10-HCPT injections. The 10-HCPT nanocrystals also showed enhanced drug accumulation in tumors and better anticancer efficacy in 4T1-bearing mice. In summary, the 10-HCPT nanocrystals prepared in this study seem to be a promising delivery system for a new form of 10-HCPT dosages.

show abstract

In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions

Abstract: Submicron emulsions can alter the pharmacokinetic characteristics and tissue distribution of HCPT, and enhance tumour targeting and anti-tumour activity.

Cited by 10 publications

References 21 publications

Hydroxycamptothecin Nanorods Prepared by Fluorescently Labeled Oligoethylene Glycols (OEG) Codendrimer: Antitumor Efficacy in Vitro and in Vivo

Hydroxycamptothecin Nanorods Prepared by Fluorescently Labeled Oligoethylene Glycols (OEG) Codendrimer: Antitumor Efficacy in Vitro and in Vivo

Anti-tumour Effect and Pharmacokinetics of an Active Ingredient Isolated from <i>Inonotus hispidus</i>

A stabilizer-free and organic solvent-free method to prepare 10-hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation

Contact Info

Product

Resources

About