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Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer.

Cuong NV, Jiang JL, Li YL, Chen JR, Jwo SC, Hsieh MF - Cancers (Basel) (2010)

Bottom Line: A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice.Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats.Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan. mfhsieh@cycu.edu.tw.

ABSTRACT
The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε‑caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

No MeSH data available.


Related in: MedlinePlus

Biodistribution of DOX-loaded micelle (a) and free DOX (b) after administration at the equivalent 5 mg/kg DOX. Each bar represents the mean of three measurements ± S.D. Bars marked with * (p < 0.05) are significantly different between 1 h time-point and 4 and 8 h. Bars marked with ** and *** correspond to p values 0.073 and 0.065, respectively.
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f8-cancers-03-00061: Biodistribution of DOX-loaded micelle (a) and free DOX (b) after administration at the equivalent 5 mg/kg DOX. Each bar represents the mean of three measurements ± S.D. Bars marked with * (p < 0.05) are significantly different between 1 h time-point and 4 and 8 h. Bars marked with ** and *** correspond to p values 0.073 and 0.065, respectively.

Mentions: Biodistribution profile of free DOX and DOX-loaded micelles were examined in Wistar rat. The animal was intravenously administered a dose of 5 mg/kg DOX equivalent. DOX content in plasma, heart, liver, lung, kidney and spleen were measured at three intervals (1, 4 and 8 h). The results indicated that DOX-loaded micelle could prolong the DOX in plasma and exhibited higher DOX concentration in plasma than free DOX (Figure 8). At the 1 and 4 h time-points, the DOX level of DOX-loaded micelle in plasma was 2.3 and 3.6-fold higher than that of free DOX, respectively. Interestingly, at 8 h time-point, the DOX level of free DOX was not detected in plasma, in contrast, it still remained at high concentration in DOX-loaded micelle formulation. Biodistribution patterns to the hearts, lungs, and kidneys did not show substantial accumulation in DOX-loaded micelle and free DOX groups and were not significantly different. The uptake by liver was observed to be higher for free DOX as compared to DOX-loaded micelle at 1 h post-injection.


Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer.

Cuong NV, Jiang JL, Li YL, Chen JR, Jwo SC, Hsieh MF - Cancers (Basel) (2010)

Biodistribution of DOX-loaded micelle (a) and free DOX (b) after administration at the equivalent 5 mg/kg DOX. Each bar represents the mean of three measurements ± S.D. Bars marked with * (p < 0.05) are significantly different between 1 h time-point and 4 and 8 h. Bars marked with ** and *** correspond to p values 0.073 and 0.065, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756349&req=5

f8-cancers-03-00061: Biodistribution of DOX-loaded micelle (a) and free DOX (b) after administration at the equivalent 5 mg/kg DOX. Each bar represents the mean of three measurements ± S.D. Bars marked with * (p < 0.05) are significantly different between 1 h time-point and 4 and 8 h. Bars marked with ** and *** correspond to p values 0.073 and 0.065, respectively.
Mentions: Biodistribution profile of free DOX and DOX-loaded micelles were examined in Wistar rat. The animal was intravenously administered a dose of 5 mg/kg DOX equivalent. DOX content in plasma, heart, liver, lung, kidney and spleen were measured at three intervals (1, 4 and 8 h). The results indicated that DOX-loaded micelle could prolong the DOX in plasma and exhibited higher DOX concentration in plasma than free DOX (Figure 8). At the 1 and 4 h time-points, the DOX level of DOX-loaded micelle in plasma was 2.3 and 3.6-fold higher than that of free DOX, respectively. Interestingly, at 8 h time-point, the DOX level of free DOX was not detected in plasma, in contrast, it still remained at high concentration in DOX-loaded micelle formulation. Biodistribution patterns to the hearts, lungs, and kidneys did not show substantial accumulation in DOX-loaded micelle and free DOX groups and were not significantly different. The uptake by liver was observed to be higher for free DOX as compared to DOX-loaded micelle at 1 h post-injection.

Bottom Line: A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice.Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats.Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan. mfhsieh@cycu.edu.tw.

ABSTRACT
The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε‑caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

No MeSH data available.


Related in: MedlinePlus