Inflammation-Targeted Delivery of Celastrol via Neutrophil Membrane-Coated Nanoparticles in the Management of Acute Pancreatitis

Mol Pharm. 2019 Mar 4;16(3):1397-1405. doi: 10.1021/acs.molpharmaceut.8b01342. Epub 2019 Feb 21.

Abstract

Celastrol (CLT)-loaded PEG-PLGA nanoparticles (NPs/CLT) coated with neutrophil membranes (NNPs/CLT) were explored for the management of acute pancreatitis (AP). PEG-PLGA nanoparticles sized around 150 nm were proven to selectively accumulate in the pancreas in rats with AP. NNPs were found to overcome the blood-pancreas barrier and specifically distributed to the pancreatic tissues. Moreover, NNPs showed more selective accumulation in the pancreas than nanoparticles without any membrane coating in AP rats. Compared to CLT solution and the NPs/CLT group, NNPs/CLT significantly downregulated the levels of serum amylase and pancreatic myeloperoxidase in AP rats. Also, using NNPs as the delivery vehicle significantly reduced the systemic toxicity of CLT in AP rats. Together, these results suggest that NNPs/CLT represent a highly promising delivery vehicle for the targeted therapy of AP.

Keywords: PEG−PLGA nanoparticles; acute pancreatitis; celastrol; neutrophil membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amylases / blood
  • Animals
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Disease Models, Animal
  • Inflammation / drug therapy*
  • Interleukin-6 / blood
  • Lung Injury / drug therapy
  • Lung Injury / etiology
  • Male
  • Molecular Targeted Therapy / methods
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Neutrophils / cytology*
  • Pancreatitis / complications
  • Pancreatitis / diagnostic imaging
  • Pancreatitis / drug therapy*
  • Particle Size
  • Pentacyclic Triterpenes
  • Pharmaceutical Vehicles / chemistry
  • Pharmaceutical Vehicles / metabolism*
  • Polyesters / chemistry
  • Polyesters / metabolism
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Treatment Outcome
  • Triterpenes / chemistry*
  • Triterpenes / metabolism
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Il6 protein, rat
  • Interleukin-6
  • Pentacyclic Triterpenes
  • Pharmaceutical Vehicles
  • Polyesters
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols
  • Amylases
  • celastrol