Synthesis and therapeutic effect of styrene-maleic acid copolymer-conjugated pirarubicin.
Bottom Line: Consequently, SMA-THP conjugate showed significantly prolonged circulation time compared to free THP and high tumor-targeting efficiency by the enhanced permeability and retention (EPR) effect.As a result, remarkable antitumor effect was achieved against two types of tumors in mice without apparent adverse effects.These findings suggest the potential of SMA-THP conjugate as a highly favorable candidate for anticancer nanomedicine with good stability and tumor-targeting properties in vivo.
Affiliation: Institute for Drug Delivery Science, Sojo University, Kumamoto, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.Show MeSH
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Mentions: Figure1 shows a scheme of the synthesis of SMA-THP conjugate. The amino group of THP was used to react with the maleic anhydride residue of SMA to form an amide bond. Briefly, 200 mg SMA anhydride and 100 mg THP were mixed in 10 mL N,N-dimethylformamide (DMF) followed by addition of 20 μL triethylamine. The reaction was carried out under stirring for 24 h at room temperature in the dark. After the reaction, SMA-THP conjugates were precipitated and washed by diethyl ether, which was then purified by gel permeation chromatography (Bio-Beads SX-1; Bio-Rad, Hercules, CA, USA; φ = 30 mm, L = 250 mm) to remove unreacted THP using DMF as an eluate. Then 0.1 M NaHCO3 (pH 8.2) was added to SMA-THP conjugate to hydrolyze remaining maleic anhydride residues, followed by dialysis against distilled water and ultrafiltration (Millipore, Bedford, MA, USA) with a 50-kDa cut-off membrane, and then lyophilization.
Affiliation: Institute for Drug Delivery Science, Sojo University, Kumamoto, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.