Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery

Autor: Pan He, Yusheng Li, Dong Wang, Bingtong Tang, Yu Zhang, Peng She, Chunsheng Xiao, Xin Ming Liu, Xin Guo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Nanomedicine
ISSN: 1178-2013
1176-9114
Popis: Pan He,1 Bingtong Tang,1 Yusheng Li,1 Yu Zhang,2 Xinming Liu,2 Xin Guo,1 Dong Wang,3 Peng She,3,4 Chunsheng Xiao2 1School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China; 3Department of Orthopaedics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 4Joint Surgery Department, The First Hospital, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Pan He; Peng SheSchool of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of ChinaTel +86-431-85583188Fax +86-431-85583188Email hepan@cust.edu.cn; shep@mail.sysu.edu.cnBackground: 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.Keywords: oxidation responsiveness, PEGylated polyesters, nanosized micelles, anti-inflammatory therapy, curcumin delivery
Databáze: OpenAIRE
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