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

Int J Nanomedicine. 2021 Jul 27:16:5053-5064. doi: 10.2147/IJN.S311718. eCollection 2021.

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.

Keywords: PEGylated polyesters; anti-inflammatory therapy; curcumin delivery; nanosized micelles; oxidation responsiveness.

MeSH terms

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

Substances

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