Celastrol-loaded PEG-: B -PPS nanocarriers as an anti-inflammatory treatment for atherosclerosis

Sean D. Allen, Yu Gang Liu, Taehyeung Kim, Sharan Bobbala, Sijia Yi, Xiaohan Zhang, Jaehyuk Choi, Evan A. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

In this work, the hydrophobic small molecule NF-κB inhibitor celastrol was loaded into poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) micelles. PEG-b-PPS micelles demonstrated high loading efficiency, low polydispersity, and no morphological changes upon loading with celastrol. Encapsulation of celastrol within these nanocarriers significantly reduced cytotoxicity compared to free celastrol, while simultaneously expanding the lower concentration range for effective inhibition of NF-κB signaling by nearly 50000-fold. Furthermore, celastrol-loaded micelles successfully reduced TNF-α secretion after LPS stimulation of RAW 264.7 cells and reduced the number of neutrophils and inflammatory monocytes within atherosclerotic plaques of ldlr -/- mice. This reduction in inflammatory cells was matched by a reduction in plaque area, suggesting that celastrol-loaded nanocarriers may serve as an anti-inflammatory treatment for atherosclerosis.

Original languageEnglish (US)
Pages (from-to)657-668
Number of pages12
JournalBiomaterials Science
Volume7
Issue number2
DOIs
StatePublished - Feb 2019

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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