alexa SMA-doxorubicin, a new polymeric micellar drug for effective targeting to solid tumours.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Greish K, Sawa T, Fang J, Akaike T, Maeda H

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Abstract Copolymer of styrene-maleic acid (SMA) was used to construct micelles containing doxorubicin by means of a hydrophobic interaction between the styrene moiety of SMA and doxorubicin (Dox). The micelles obtained (SMA-Dox) showed a high solubility in water and a constant doxorubicin release rate of about 3-4\%/day in vitro. The SMA-Dox micelle preparation was less (36-70\%) cytotoxic to the SW480 human colon cancer cell line in vitro compared with free doxorubicin. In vivo assay of SMA-Dox in ddY mice bearing S-180 tumor revealed a potent anticancer effect with no remarkable toxicity up to a dose of 100 mg/kg of free doxorubicin equivalent. The drug concentration in tumor after administration of SMA-Dox was 13 times higher than that after the free drug. This result can be attributed to the enhanced permeability and retention (EPR) effect of macromolecular drugs observed in solid tumors. Complete blood counts and cardiac histology showed no serious side effects for intravenous (i.v.) doses of the micellar formulation as high as 100 mg/kg doxorubicin equivalent in mice. These data indicate that i.v. administration of SMA-Dox micellar formulation can enhance the therapeutic effect of doxorubicin while reducing greatly cardiac and bone marrow toxicity, which should allow safe use of high doses of this agent. Copyright 2004 Elsevier B.V. This article was published in J Control Release and referenced in Journal of Nanomedicine & Nanotechnology

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