1. In situ grafting of PEG Acrylate on drugs with aliphatic hydroxyl functionalities via RAFT polymerization to synthesize drug/polymer conjugates with improved water solubility.
- Author
-
Feng, Zhonghan, Wang, Huining, Liu, Maosheng, Chen, Tao, Liu, Yan, Xu, Wenying, Wang, Haiyan, and Liu, Jingquan
- Subjects
- *
DRUG therapy , *DRUG efficacy , *ANTINEOPLASTIC agents , *POLYMERIZATION , *ACRYLATES - Abstract
• Mitoxantrone is modified with PEG-A via RAFT polymerization. • The solubility of MTX/PPEG-A can be improved by 550% compared to the unmodified MTX. • Cytotoxicity and drug efficacy of MTX/PPEG-A are comparable to the unmodified MTX. • MTX/PPEG-A can be degraded into MTX with full drug efficacy via enzymatic catalysis. Despite the fact that mitoxantrone (MTX) is an effective prescription drug for cancer therapy, its poor water solubility is a great challenge that limits its practical applications. Herein, to overcome this shortcoming, a drug/polymer conjugate of MTX with poly (ethyleneglycol) acrylate (PEG-A) (MTX/PPEG-A) was developed via in situ reversible addition-fragmentation chain transfer (RAFT) polymerization. Impressively, the MTX/PPEG-A conjugate shows highly improved water solubility, which is about 550% that of the unmodified MTX. The synthesized MTX/PPEG-A conjugate drug efficacy can be maintained and cytotoxicity reduced slightly compared with the unmodified MTX. In addition, the MTX/PPEG-A can be hydrolyzed by the esterase into pristine MTX with restored drug efficacy in vivo. All in all, the significant improvement of the water solubility and the slightly improved biocompatibility of MTX/PPEG-A will be well-suited for the administration and delivery of anti-cancer drugs in cancer therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF