International journal of nanomedicine · 2021
Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery.
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He Pan, Tang Bingtong, Li Yusheng, Zhang Yu, Liu Xinming, Guo Xin, Wang Dong, She Peng, Xiao Chunsheng
Аннотация
BACKGROUND: High levels of oxidants, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are typical characteristics of an inflammatory microenvironment and are closely associated with a various inflammatory pathologies, eg, cancer, diabetes, atherosclerosis, and neurodegenerative diseases. Therefore, the delivery of anti-inflammatory drugs by oxidation-responsive smart systems would be an efficient anti-inflammatory strategy that benefits from the selective drug release in an inflammatory site, a lower treatment dose, and minimizes side effects.
PURPOSE: In this study, we present the feasibility of an oxidation-sensitive PEGylated alternating polyester, methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), as novel nanocarrier for curcumin (CUR), and explore the application in anti-inflammatory therapy.
METHODS: The copolymers used were obtained by combining a click reaction and a ring-opening-polymerization method. CUR was loaded by self-assembly. The in vitro drug release, cytotoxicity toward RAW 264.7 cells and cellular uptake were investigated. Furthermore, the anti-inflammatory effects of CUR-loaded polymeric nanoparticles (NPs-CUR) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and tested in a murine model of ankle inflammation.
RESULTS: Fast drug release from NPs-CUR was observed in trigger of 1 mM H2O2 in PBS. Compared with NPs and free drugs, the significant anti-inflammatory potential of NPs-CUR was proven in activated RAW 264.7 cells by inhibiting the production of TNF-α, IL-1β, and IL-6 and increasing the level of an anti-inflammatory cytokine IL-10. Finally, a local injection of NPs-CUR at a dose of 0.25 mg/kg suppressed the acute ankle inflammatory response in mice by histological observation and further reduced the expression of pro-inflammatory cytokines in the affected ankle joints compared to that of free CUR.
CONCLUSION: Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.
PURPOSE: In this study, we present the feasibility of an oxidation-sensitive PEGylated alternating polyester, methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), as novel nanocarrier for curcumin (CUR), and explore the application in anti-inflammatory therapy.
METHODS: The copolymers used were obtained by combining a click reaction and a ring-opening-polymerization method. CUR was loaded by self-assembly. The in vitro drug release, cytotoxicity toward RAW 264.7 cells and cellular uptake were investigated. Furthermore, the anti-inflammatory effects of CUR-loaded polymeric nanoparticles (NPs-CUR) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and tested in a murine model of ankle inflammation.
RESULTS: Fast drug release from NPs-CUR was observed in trigger of 1 mM H2O2 in PBS. Compared with NPs and free drugs, the significant anti-inflammatory potential of NPs-CUR was proven in activated RAW 264.7 cells by inhibiting the production of TNF-α, IL-1β, and IL-6 and increasing the level of an anti-inflammatory cytokine IL-10. Finally, a local injection of NPs-CUR at a dose of 0.25 mg/kg suppressed the acute ankle inflammatory response in mice by histological observation and further reduced the expression of pro-inflammatory cytokines in the affected ankle joints compared to that of free CUR.
CONCLUSION: Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.