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 language | English (US) |
|---|---|
| Pages (from-to) | 657-668 |
| Number of pages | 12 |
| Journal | Biomaterials Science |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2019 |
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ASJC Scopus subject areas
- Biomedical Engineering
- Materials Science(all)
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Celastrol-loaded PEG- : B -PPS nanocarriers as an anti-inflammatory treatment for atherosclerosis. / Allen, Sean D.; Liu, Yu Gang; Kim, Taehyeung; Bobbala, Sharan; Yi, Sijia; Zhang, Xiaohan; Choi, Jaehyuk; Scott, Evan A.
In: Biomaterials Science, Vol. 7, No. 2, 02.2019, p. 657-668.Research output: Contribution to journal › Article
TY - JOUR
T1 - Celastrol-loaded PEG-
T2 - B -PPS nanocarriers as an anti-inflammatory treatment for atherosclerosis
AU - Allen, Sean D.
AU - Liu, Yu Gang
AU - Kim, Taehyeung
AU - Bobbala, Sharan
AU - Yi, Sijia
AU - Zhang, Xiaohan
AU - Choi, Jaehyuk
AU - Scott, Evan A.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060650526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060650526&partnerID=8YFLogxK
U2 - 10.1039/c8bm01224e
DO - 10.1039/c8bm01224e
M3 - Article
C2 - 30601470
AN - SCOPUS:85060650526
VL - 7
SP - 657
EP - 668
JO - Biomaterials Science
JF - Biomaterials Science
SN - 2047-4830
IS - 2
ER -