A Novel Facile and Efficient Prophylaxis Avenue of Chitosan Oligosaccharide/PLGA Based Polydatin Loaded Nanoparticles Against Bleomycin-Induced Lung Inflammation in Experimental Rat Model

AAPS PharmSciTech. 2025 Jan 16;26(1):35. doi: 10.1208/s12249-024-03022-2.

Abstract

Lung inflammation is a hallmark of several respiratory diseases. Despite the great effectiveness of the synthetic antiinflammatory agents, they cause potential side effects. Polydatin (PD), a natural phytomedicine, has antioxidant and antiinflammatory effects. Its clinical applications are hindered due to poor aqueous solubility, low bioavailability, and rapid metabolism by first-pass effect. Herein, we report the development of a novel chitosan oligosaccharide-coated PD-loaded Poly dl-lactide-co-glycolide nanoparticles (COS-coated PD/PLGA NPs) against a bleomycin-induced pulmonary inflammation in a rat model. The NPs exhibited a small particle size of 188.57 ± 5.68 nm and a high zeta potential of + 18.13 ± 2.75 mV with spherical architecture and sustained release pattern of PD. In vivo studies in bleomycin-induced lung inflammation in a rat model revealed the superior prophylactic activity of COS-coated PD/PLGA NPs over the free drug (PD) as demonstrated by histopathological and immunohistochemical analyses, alongside biochemical assays evaluating oxidative stress biomarkers and inflammatory cytokine levels. Overall, the optimized COS-coated PD/PLGA NPs formulation offers a promising prophylactic platform against many respiratory diseases.

Keywords: PLGA; antiinflammatory; chitosan oligosaccharide; lung inflammation; polydatin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Bleomycin*
  • Chitosan* / chemistry
  • Disease Models, Animal*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Glucosides* / administration & dosage
  • Glucosides* / chemistry
  • Glucosides* / pharmacology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Nanoparticles* / chemistry
  • Oligosaccharides* / administration & dosage
  • Oligosaccharides* / chemistry
  • Oligosaccharides* / pharmacology
  • Oxidative Stress / drug effects
  • Particle Size
  • Pneumonia* / chemically induced
  • Pneumonia* / drug therapy
  • Pneumonia* / metabolism
  • Pneumonia* / prevention & control
  • Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Stilbenes* / administration & dosage
  • Stilbenes* / chemistry
  • Stilbenes* / pharmacology

Substances

  • Chitosan
  • polydatin
  • Glucosides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Stilbenes
  • Bleomycin
  • Oligosaccharides
  • Drug Carriers
  • Anti-Inflammatory Agents