XiuquanQuan, Lin Kang(co-first author), Xuezhe Yin, ZhehuJin, Zhonggao Gao^*, Synthesis of PEGylated hyaluronic acid for loading dichloro(1,2-diaminocyclohexane) platinum(II) (DACHPt) in nanoparticles for cancer treatment, Chinese Chemical Letters 26 (2015) 695-699.

Abstract

Dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt), a cisplatin (CDDP) analog, has shown lower toxicity than CDDP and no cross-resistance with CDDP in many CDDP-resistant cancers. PEGylated hyaluronan (mPEG-HA) is an mPEG conjugated with hyaluronan biodegradable polymer which is a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. mPEG-hyaluronan–DACHPt (PEG-HA–Pt) conjugate could circulate long-term in the bloodstream and increase DACHPt concentration in the tumor site and decrease systemic toxicity. mPEG-HA conjugates with the range of 1%–5% substitution were synthesized, and the structures were confirmed by 1H NMR and IR. The particle size of DACHPt incorporated with mPEG-HA was about 86 nm and the loading content and efficiency were about 19% (w/w) and 86%, respectively. The synthesized mPEG-HA with different PEG substitution degrees presented non toxicity, and the cell viability of DACHPt loaded in mPEG-HA nanoparticles increased with increasing doses of DACHPt. DACHPt release from nanoparticles slightly decreased with increasing PEG substitution degree from 1% to 5% at 37 °C, pH 7.4 PBS solution. The DACHPt loaded in mPEG-HA nanoparticles significantly inhibited the growth of A549 xenografts in nude mice when compared to the DACHPt loaded in HA nanoparticles and the control group after 4 weeks treatment (p < 0.01 compared with control). The body weight change curve shows that the mice weight loss was less than 5% by treating with both DACHPt loaded in mPEG-HA and HA nanoparticles. In conclusion, a novel DACHPt loaded mPEG-HA delivery system was developed with sustained release and increased platinum concentration in the tumor.

Keywords: DACHPt PEGylated hyaluronan A549 lung cancer cell

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