Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery.
Diblock copolymers of poly(epsilon-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 microg ml(-1), while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 degrees 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.
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Xintao
X
Shuai
Hua
H
Ai
Norased
N
Nasongkla
Saejeong
S
Kim
Jinming
J
Gao
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008823:Micelles; D018613:Microscopy, Confocal; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin