Limits...
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

Hemolytic test on PEG-PCL-PEG micelle and DOX-loaded PEG-PCL-PEG micelle. Data represents the mean ± standard error of the mean of three experiments (p < 0.01 compared to saline group).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3756349&req=5

f3-cancers-03-00061: Hemolytic test on PEG-PCL-PEG micelle and DOX-loaded PEG-PCL-PEG micelle. Data represents the mean ± standard error of the mean of three experiments (p < 0.01 compared to saline group).

Mentions: Furthermore, the biocompatibilities of PEG-PCL-PEG micelle and DOX-loaded PEG-PCL-PEG micelle in the presence of red blood cells (RBCs) were examined by a hemolytic test. As shown in Figure 3, the percentage of hemolysis increased accordingly with the concentration of micelle. DOX-unloaded polymeric micelle at a concentration of 2 mg/mL caused a slight increase in hemolysis when compared with that of the negative control (saline solution) and blank solution (PBS buffer). However, DOX-loaded micelle exhibited higher hemolytic activity than that of DOX-unloaded PEG-PCL-PEG micelle. This may be attributed to the release of DOX in medium that caused hemolysis. The results also demonstrated that the hemolytic activity of micellar DOX depended on the DOX concentration. DOX concentrations were 157, 78.5, 39.2 and 7.85 μg/mL for 2.0, 1.0, 0.5 and 0.1 mg/mL polymeric micelle, respectively.


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)

Hemolytic test on PEG-PCL-PEG micelle and DOX-loaded PEG-PCL-PEG micelle. Data represents the mean ± standard error of the mean of three experiments (p < 0.01 compared to saline group).
© Copyright Policy
Related In: Results  -  Collection

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

f3-cancers-03-00061: Hemolytic test on PEG-PCL-PEG micelle and DOX-loaded PEG-PCL-PEG micelle. Data represents the mean ± standard error of the mean of three experiments (p < 0.01 compared to saline group).
Mentions: Furthermore, the biocompatibilities of PEG-PCL-PEG micelle and DOX-loaded PEG-PCL-PEG micelle in the presence of red blood cells (RBCs) were examined by a hemolytic test. As shown in Figure 3, the percentage of hemolysis increased accordingly with the concentration of micelle. DOX-unloaded polymeric micelle at a concentration of 2 mg/mL caused a slight increase in hemolysis when compared with that of the negative control (saline solution) and blank solution (PBS buffer). However, DOX-loaded micelle exhibited higher hemolytic activity than that of DOX-unloaded PEG-PCL-PEG micelle. This may be attributed to the release of DOX in medium that caused hemolysis. The results also demonstrated that the hemolytic activity of micellar DOX depended on the DOX concentration. DOX concentrations were 157, 78.5, 39.2 and 7.85 μg/mL for 2.0, 1.0, 0.5 and 0.1 mg/mL polymeric micelle, respectively.

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