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Synthesis and therapeutic effect of styrene-maleic acid copolymer-conjugated pirarubicin.

Tsukigawa K, Liao L, Nakamura H, Fang J, Greish K, Otagiri M, Maeda H - Cancer Sci. (2015)

Bottom Line: The SMA-THP conjugate also formed micelles and showed albumin binding capacity in aqueous solution, which suggested that this conjugate behaved as a macromolecule during blood circulation.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Drug Delivery Science, Sojo University, Kumamoto, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.

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Related in: MedlinePlus

Synthesis of styrene–maleic acid copolymer (SMA)-conjugated pirarubicin (THP) (SMA-THP conjugate). Chemical structures and conjugation pathway. DMF, N,N-dimethylformamide.
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fig01: Synthesis of styrene–maleic acid copolymer (SMA)-conjugated pirarubicin (THP) (SMA-THP conjugate). Chemical structures and conjugation pathway. DMF, N,N-dimethylformamide.

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.


Synthesis and therapeutic effect of styrene-maleic acid copolymer-conjugated pirarubicin.

Tsukigawa K, Liao L, Nakamura H, Fang J, Greish K, Otagiri M, Maeda H - Cancer Sci. (2015)

Synthesis of styrene–maleic acid copolymer (SMA)-conjugated pirarubicin (THP) (SMA-THP conjugate). Chemical structures and conjugation pathway. DMF, N,N-dimethylformamide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376435&req=5

fig01: Synthesis of styrene–maleic acid copolymer (SMA)-conjugated pirarubicin (THP) (SMA-THP conjugate). Chemical structures and conjugation pathway. DMF, N,N-dimethylformamide.
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.

Bottom Line: The SMA-THP conjugate also formed micelles and showed albumin binding capacity in aqueous solution, which suggested that this conjugate behaved as a macromolecule during blood circulation.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Drug Delivery Science, Sojo University, Kumamoto, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.

Show MeSH
Related in: MedlinePlus