Novel polyurethane-based nanoparticles of infliximab to reduce inflammation in an in-vitro intestinal epithelial barrier model

Int J Pharm. 2019 Jun 30:565:533-542. doi: 10.1016/j.ijpharm.2019.05.025. Epub 2019 May 11.

Abstract

In this study we examined the potential of novel biodegradable polymers of polyesterurethane (PU), and its PEGylated (PU-PEG) form as nanocarriers of Infliximab (INF), to treat inflammation in an in-vitro epithelial model. Nanoparticles (NPs) formulated were of average size of 200-287 nm. INF loading of NPs (INF-NPs) resulted in an increase in size and zeta potential. No cytotoxicity was observed for any of the NPs. Cellular interaction and uptake of PU NPs were similar compared with polycaprolactone (PCL) NPs and significantly higher to Poly(lactic-co-glycolic) acid (PLGA) NPs. Cellular interaction was higher for corresponding PEG-NPs. INF-PU and INF-PU-PEG NPs showed a rapid rate and extent of recovery of the epithelial barrier function in inflamed Caco-2 cell monolayers and decreased cytokine levels in inflamed monocytes. Results obtained in this study are promising and the potential of PU and PU-PEG NPs for drug delivery and targeting to treat gastrointestinal inflammation warrants further investigation.

Keywords: Caco-2; Cellular uptake; IBD; Inflammation; Infliximab; Nanoparticles; TNF-α.

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage*
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Drug Carriers / administration & dosage*
  • Humans
  • Infliximab / administration & dosage*
  • Interleukin-8 / immunology
  • Intestinal Mucosa / metabolism
  • Lipopolysaccharides
  • Monocytes / drug effects
  • Monocytes / immunology
  • Nanoparticles / administration & dosage*
  • Polyurethanes / administration & dosage*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • CXCL8 protein, human
  • Drug Carriers
  • Interleukin-8
  • Lipopolysaccharides
  • Polyurethanes
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Infliximab