Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer.

Abstract

Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ≈25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect.

• Authors: Xiang Gao, BiLan Wang, XiaWei Wei, Wang Rao, Fang Ai, Fen Zhao, Ke Men, Bowen Yang, Xingyu Liu, Meijuan Huang, Maling Gou, ZhiYong Qian, Ning Huang, Yuquan Wei
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 8 Pg. 971-82 ( 2013) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 23493403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Ethylene Glycols
• Micelles
• Polyesters
• poly(epsilon-caprolactone)-b-poly(ethylene glycol)
• polycaprolactone
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry)
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (administration & dosage, chemistry)
• Drug Carriers (administration & dosage, chemistry)
• Ethylene Glycols (administration & dosage, chemistry)
• Female
• Hemolysis (drug effects)
• Mice
• Mice, Inbred BALB C
• Micelles
• Neoplasms, Experimental (pathology)
• Particle Size
• Polyesters (administration & dosage, chemistry)
• Rabbits
• Xenograft Model Antitumor Assays