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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

Antitumor effect of free DOX and DOX-loaded micelle in MCF-7 tumor bearing mice. Mice were administered PBS (●) and free DOX (■) and DOX-loaded micelle (▲) i.v at the equivalent 5 mg/kg DOX.
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f9-cancers-03-00061: Antitumor effect of free DOX and DOX-loaded micelle in MCF-7 tumor bearing mice. Mice were administered PBS (●) and free DOX (■) and DOX-loaded micelle (▲) i.v at the equivalent 5 mg/kg DOX.

Mentions: The antitumor efficacy of free DOX and DOX-loaded micelles was examined with MCF-7 human breast tumor bearing nude mice. The tumor growth rates of mice treated with free DOX, DOX-loaded micelle and PBS are presented in Figure 9. The free DOX and DOX-loaded micelle exhibited similar effectiveness in preventing tumor growth when mice were administered with single dose (data not shown). However, when the mice were treated with three injections, the DOX-loaded micelle demonstrated the greater growth inhibition of tumor volume in comparison to free DOX. Tumor volumes were decreased up to 60.0% by DOX-loaded micelle and 45.4% by free DOX, compared to that of control group, respectively (Figure 9). Based on the above results, DOX-loaded micelle showed higher tumor targeting efficiency and more therapeutic effects than free DOX. Hence, the hydrophobic drug encapsulated in PEG-PCL-PEG micelle has advantages of prolonged blood circulation, RES uptake prevention, and passive targeting of polymeric micelles to tumor tissue through EPR effect [14,33].


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)

Antitumor effect of free DOX and DOX-loaded micelle in MCF-7 tumor bearing mice. Mice were administered PBS (●) and free DOX (■) and DOX-loaded micelle (▲) i.v at the equivalent 5 mg/kg DOX.
© Copyright Policy
Related In: Results  -  Collection

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

f9-cancers-03-00061: Antitumor effect of free DOX and DOX-loaded micelle in MCF-7 tumor bearing mice. Mice were administered PBS (●) and free DOX (■) and DOX-loaded micelle (▲) i.v at the equivalent 5 mg/kg DOX.
Mentions: The antitumor efficacy of free DOX and DOX-loaded micelles was examined with MCF-7 human breast tumor bearing nude mice. The tumor growth rates of mice treated with free DOX, DOX-loaded micelle and PBS are presented in Figure 9. The free DOX and DOX-loaded micelle exhibited similar effectiveness in preventing tumor growth when mice were administered with single dose (data not shown). However, when the mice were treated with three injections, the DOX-loaded micelle demonstrated the greater growth inhibition of tumor volume in comparison to free DOX. Tumor volumes were decreased up to 60.0% by DOX-loaded micelle and 45.4% by free DOX, compared to that of control group, respectively (Figure 9). Based on the above results, DOX-loaded micelle showed higher tumor targeting efficiency and more therapeutic effects than free DOX. Hence, the hydrophobic drug encapsulated in PEG-PCL-PEG micelle has advantages of prolonged blood circulation, RES uptake prevention, and passive targeting of polymeric micelles to tumor tissue through EPR effect [14,33].

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