Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis

Eur J Pharm Biopharm. 2024 Jun:199:114309. doi: 10.1016/j.ejpb.2024.114309. Epub 2024 May 3.

Abstract

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

Keywords: Colon-targeted gel beads; Molecular simulation; Partially oxidized sodium alginate; Pharmacodynamics; Pharmacokinetics; Pulsatilla saponins.

MeSH terms

  • Administration, Oral
  • Alginates* / chemistry
  • Animals
  • Chitosan* / chemistry
  • Colitis, Ulcerative* / drug therapy
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Disease Models, Animal
  • Drug Delivery Systems* / methods
  • Gels*
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Microspheres*
  • Particle Size
  • Polymers / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Saponins* / administration & dosage
  • Saponins* / chemistry
  • Saponins* / pharmacology