Synthesis and therapeutic effect of styrene-maleic acid copolymer-conjugated pirarubicin.
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.
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: As shown in Figure4(a), free THP was cleared rapidly from blood circulation after i.v. injection, whereas SMA-THP conjugate remained high in blood circulation for a much longer time, with a 24.5-fold higher concentration curve than free THP. At 24¬†h after i.v. injection (Fig.4b), free THP showed the highest concentration in spleen, followed by liver; the accumulation in tumor was very low, at approximately 13% of that in spleen. Accumulation of SMA-THP conjugate was highest in liver, while drug levels in tumor were higher than most other normal tissues. The high accumulation in liver is similar to previous SMA-conjugated drugs (e.g. SMANCS) as well as other macromolecular drugs, mostly through the reticuloendothelial system (e.g. macrophages).5,18 In addition, high accumulation of SMA-THP conjugate in kidney was also observed, which is probably due to the disintegrated chemical unit of SMA-THP conjugate from micelles whose molecular size (approximately 2200) is smaller than the renal threshold (40¬†kDa).
Affiliation: Institute for Drug Delivery Science, Sojo University, Kumamoto, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.