Programmable Polymeric Microneedles for Combined Chemotherapy and Antioxidative Treatment of Rheumatoid Arthritis

ACS Appl Mater Interfaces. 2021 Nov 24;13(46):55559-55568. doi: 10.1021/acsami.1c17375. Epub 2021 Nov 16.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Antioxidative treatment combined with chemotherapy holds great promise for RA treatment, and the ability to efficiently deliver drugs and antioxidants to the RA synovial joint is highly desired. Herein, we developed a programmable polymeric microneedle (MN) platform for transdermal delivery of methotrexate (MTX) and reactive oxygen species (ROS) scavengers for RA treatment. The biodegradable MNs made of polyvinylpyrrolidone (PVP) were incorporated with polydopamine/manganese dioxide (termed PDA@MnO2) and MTX. After insertion into skin tissue, the MNs degraded, thus enabling release of loaded MTX and PDA@MnO2. The PDA@MnO2 could be utilized as an MRI contrast agent in the RA synovial microenvironment. It also acted as a robust antioxidant to remove ROS and decrease RA inflammation, which when combined with the MTX-mediated chemotherapy led to an ideal outcome for RA treatments in a murine model. This work not only represents a valuable MN-assisted RA therapeutic agent transdermal delivery approach but also opens a new avenue for chemotherapy and antioxidative synergistic treatment of RA.

Keywords: antioxidative; chemotherapy; microneedles; rheumatoid arthritis.

MeSH terms

  • 3T3 Cells
  • Administration, Cutaneous
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Drug Therapy, Combination
  • Indoles / administration & dosage
  • Indoles / therapeutic use
  • Manganese Compounds / administration & dosage
  • Manganese Compounds / therapeutic use
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Mice
  • Oxides / administration & dosage
  • Oxides / therapeutic use
  • Particle Size
  • Polymers / administration & dosage
  • Polymers / therapeutic use*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Surface Properties

Substances

  • Antioxidants
  • Indoles
  • Manganese Compounds
  • Oxides
  • Polymers
  • Reactive Oxygen Species
  • polydopamine
  • manganese dioxide
  • Methotrexate