Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

Xintao Shuai; Hua Ai; Norased Nasongkla; Saejeong Kim; Jinming Gao

doi:10.1016/j.jconrel.2004.06.003

Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

Xintao Shuai, Hua Ai, Norased Nasongkla, Saejeong Kim, Jinming Gao

Research output: Contribution to journal › Article › peer-review

704 Scopus citations

Abstract

Diblock copolymers of poly(ε-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 μg ml^-1, while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37°C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.

Original language	English (US)
Pages (from-to)	415-426
Number of pages	12
Journal	Journal of Controlled Release
Volume	98
Issue number	3
DOIs	https://doi.org/10.1016/j.jconrel.2004.06.003
State	Published - Aug 27 2004

Keywords

Drug delivery
Polymer micelles

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.jconrel.2004.06.003

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title = "Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery",

abstract = "Diblock copolymers of poly(ε-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 μg ml-1, while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37°C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.",

keywords = "Drug delivery, Polymer micelles",

author = "Xintao Shuai and Hua Ai and Norased Nasongkla and Saejeong Kim and Jinming Gao",

note = "Funding Information: This research is supported by the National Institutes of Health (R01-CA-90696 to J.G.). X.T.S thanks a postdoctoral support from the Ohio Biomedical Research and Technology Trust fund.",

year = "2004",

month = aug,

day = "27",

doi = "10.1016/j.jconrel.2004.06.003",

language = "English (US)",

volume = "98",

pages = "415--426",

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T1 - Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

AU - Shuai, Xintao

AU - Ai, Hua

AU - Nasongkla, Norased

AU - Kim, Saejeong

AU - Gao, Jinming

N1 - Funding Information: This research is supported by the National Institutes of Health (R01-CA-90696 to J.G.). X.T.S thanks a postdoctoral support from the Ohio Biomedical Research and Technology Trust fund.

PY - 2004/8/27

Y1 - 2004/8/27

N2 - Diblock copolymers of poly(ε-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 μg ml-1, while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37°C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.

AB - Diblock copolymers of poly(ε-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 μg ml-1, while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37°C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.

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KW - Polymer micelles

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Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

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