pH/ROS dual-sensitive and chondroitin sulfate wrapped poly (β-amino ester)-SA-PAPE copolymer nanoparticles for macrophage-targeted oral therapy for ulcerative colitis

Nanomedicine. 2022 Jan:39:102461. doi: 10.1016/j.nano.2021.102461. Epub 2021 Sep 23.

Abstract

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.

Keywords: Curcumin; Macrophage-targeted drug delivery; Oral administration; Ulcerative colitis; pH/ROS sensitive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chondroitin Sulfates / therapeutic use
  • Colitis, Ulcerative* / drug therapy
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Drug Carriers / therapeutic use
  • Drug Delivery Systems
  • Esters / therapeutic use
  • Hydrogen-Ion Concentration
  • Macrophages / metabolism
  • Mice
  • Nanoparticles*
  • Particle Size
  • Reactive Oxygen Species

Substances

  • Drug Carriers
  • Esters
  • Reactive Oxygen Species
  • Chondroitin Sulfates
  • Curcumin