Ionically bridged dexamethasone sodium phosphate-zinc-PLGA nanocomplex in alginate microgel for the local treatment of ulcerative colitis

Arch Pharm Res. 2023 Jul;46(7):646-658. doi: 10.1007/s12272-023-01456-z. Epub 2023 Aug 3.

Abstract

Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.

Keywords: Dexamethasone; Drug delivery; Nanoparticles; Ulcerative colitis.

MeSH terms

  • Alginates / adverse effects
  • Animals
  • Colitis* / chemically induced
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / pathology
  • Colon / pathology
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Mice
  • Microgels* / therapeutic use
  • Zinc / adverse effects

Substances

  • Microgels
  • dexamethasone 21-phosphate
  • Zinc
  • Alginates
  • Dextran Sulfate