期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 15, 页码 18152-18164出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c03589
关键词
polyketals; pH-sensitive; drug delivery; nanoparticles; Cu/Zn-superoxide dismutase
资金
- National Natural Science Foundation of China [82073784]
- Industrial Technology Research and Development Projects from Development and Reform Commission of Jilin Province [2019C050-4]
The newly synthesized amphiphilic polymers can self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, and long circulation time. These materials not only exhibit better inflammation-targeting effects, but also do not induce an acidic microenvironment during degradation.
The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane(86.7%), 1,5-pentanediol(13.3%))-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.
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