Doxorubicin-loaded nanosized micelles of a star-shaped poly(ε-caprolactone)-polyphosphoester block co-polymer for treatment of human breast cancer.
Star-shaped co-polymers based on the backbone of poly(ε-caprolactone) were synthesized by a ring-opening reaction using pentaerythritol as initiator and Sn(Oct)(2) as catalyst. The star-shaped poly(ε-caprolactone) polymer was then chain extended with a terminal block of poly(ethyl ethylene phosphate) to form a copolymer, poly(ε-caprolactone)-poly(ethyl ethylene phosphate), when using the cyclic ethyl ethylene phosphate monomer. The amphiphilic block co-polymers can self-assemble into nanoscopic micelles with a mean diameter of 150 nm and a spherical shape. Additionally, the prepared micelles did not induce hemolysis and nitric oxide production in vitro based on nitric oxide, hemolytic tests and MTT assays. The hydrophobic micellar cores encapsulated doxorubicin (DOX) in an aqueous solution with a loading efficiency of 55.2%. The in vitro release of DOX from DOX-loaded micelles was pH dependent. DOX-loaded micelles present significantly enhanced cytotoxicity to both MCF-7/drug-sensitive and MCF-7/drug-resistant cells after second incubation. Moreover, results of confocal microscopy and flow cytometry of DOX-loaded micelles demonstrate the feasibility of this delivery system for effective therapy of drug-resistant tumours.
Cuong
Nguyen-Van
NV
Department of Biomedical Engineering and R&D Center for Biomedical Microdevice Technology, Chung Yuan Christian University, 200 Chung Pei Road, Chung Li, Taiwan.
Hsieh
Ming-Fa
MF
Chen
Yung-Tsung
YT
Liau
Ian
I
D000818:Animals; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D058105:Polymerization
D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C557288:poly(epsilon-caprolactone)-block-poly(ethyl ethylene phosphate); D004317:Doxorubicin