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A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.

Publication ,  Journal Article
Sinclair, SM; Bhattacharyya, J; McDaniel, JR; Gooden, DM; Gopalaswamy, R; Chilkoti, A; Setton, LA
Published in: Journal of controlled release : official journal of the Controlled Release Society
October 2013

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.

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Published In

Journal of controlled release : official journal of the Controlled Release Society

DOI

EISSN

1873-4995

ISSN

0168-3659

Publication Date

October 2013

Volume

171

Issue

1

Start / End Page

38 / 47

Related Subject Headings

  • U937 Cells
  • Sciatic Nerve
  • Pharmacology & Pharmacy
  • Peptides
  • Mice, Inbred C57BL
  • Mice
  • Intervertebral Disc Displacement
  • Inflammation
  • Humans
  • Hot Temperature
 

Citation

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Sinclair, S. M., Bhattacharyya, J., McDaniel, J. R., Gooden, D. M., Gopalaswamy, R., Chilkoti, A., & Setton, L. A. (2013). A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation. Journal of Controlled Release : Official Journal of the Controlled Release Society, 171(1), 38–47. https://doi.org/10.1016/j.jconrel.2013.06.032
Sinclair, S Michael, Jayanta Bhattacharyya, Jonathan R. McDaniel, David M. Gooden, Ramesh Gopalaswamy, Ashutosh Chilkoti, and Lori A. Setton. “A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.Journal of Controlled Release : Official Journal of the Controlled Release Society 171, no. 1 (October 2013): 38–47. https://doi.org/10.1016/j.jconrel.2013.06.032.
Sinclair SM, Bhattacharyya J, McDaniel JR, Gooden DM, Gopalaswamy R, Chilkoti A, et al. A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation. Journal of controlled release : official journal of the Controlled Release Society. 2013 Oct;171(1):38–47.
Sinclair, S. Michael, et al. “A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 171, no. 1, Oct. 2013, pp. 38–47. Epmc, doi:10.1016/j.jconrel.2013.06.032.
Sinclair SM, Bhattacharyya J, McDaniel JR, Gooden DM, Gopalaswamy R, Chilkoti A, Setton LA. A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation. Journal of controlled release : official journal of the Controlled Release Society. 2013 Oct;171(1):38–47.
Journal cover image

Published In

Journal of controlled release : official journal of the Controlled Release Society

DOI

EISSN

1873-4995

ISSN

0168-3659

Publication Date

October 2013

Volume

171

Issue

1

Start / End Page

38 / 47

Related Subject Headings

  • U937 Cells
  • Sciatic Nerve
  • Pharmacology & Pharmacy
  • Peptides
  • Mice, Inbred C57BL
  • Mice
  • Intervertebral Disc Displacement
  • Inflammation
  • Humans
  • Hot Temperature