1. Poly (l-glutamic acid)-g-methoxy poly (ethylene glycol)-gemcitabine conjugate improves the anticancer efficacy of gemcitabine.
- Author
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Yang, Chenguang, Song, Wantong, Zhang, Dawei, Yu, Haiyang, Yin, Lei, Shen, Na, Deng, Mingxiao, Tang, Zhaohui, Gu, Jingkai, and Chen, Xuesi
- Subjects
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GLUTAMIC acid , *DRUG efficacy , *PHARMACOKINETICS , *NANOPARTICLES , *ANTINEOPLASTIC agents , *CANCER treatment , *THERAPEUTICS - Abstract
Graphical abstract Abstract Gemcitabine is widely used for anticancer therapy. However, its short blood circulation time and poor stability greatly impair its application. To solve this problem, we prepared a poly (l -glutamic acid)- g -methoxy poly (ethylene glycol)-gemcitabine conjugate (l -Gem) with a 14.3 wt% drug-loading content. l -Gem showed concentration- and time-dependent cytotoxicity towards 4T1, LLC, MIA PaCa-2 and A2780 in vitro. Pharmacokinetic and biodistribution studies indicated that l -Gem had remarkably enhanced blood stability, prolonged blood circulation time and greatly improved selective tumor distribution compared with free gemcitabine. The area under the concentration–time curve from zero to infinity [AUC (0–∞) ] of l -Gem in plasma was 43-fold higher than that of free gemcitabine. The AUC (0–∞) of the inactive metabolite, 2′-deoxy-2′,2′-difluorouridine in the l -Gem group was ∼20% of that observed in the free gemcitabine group. The drug tumor accumulation ratio in the l -Gem group relative to the free gemcitabine group was 9.9 at 36 h, while the tumor AUC ratio was 15.8. Testing on Balb/C mice bearing the 4T1 tumor further demonstrated that l -Gem had significantly higher anticancer efficacy than free gemcitabine in vivo. These findings indicated that l -Gem has great potential for cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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