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

Abstract

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.

• Authors: Pan He, Bingtong Tang, Yusheng Li, Yu Zhang, Xinming Liu, Xin Guo, Dong Wang, Peng She, Chunsheng Xiao
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 16 Pg. 5053-5064 ( 2021) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 34349508 (Publication Type: Journal Article)
• Copyright: © 2021 He et al.

Chemical References

• Anti-Inflammatory Agents
• Drug Carriers
• Pharmaceutical Preparations
• Polyesters
• Polyethylene Glycols
• Hydrogen Peroxide
• Curcumin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Curcumin (pharmacology)
• Drug Carriers
• Drug Delivery Systems
• Drug Liberation
• Hydrogen Peroxide
• Mice
• Nanoparticles
• Pharmaceutical Preparations
• Polyesters (chemistry)
• Polyethylene Glycols