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

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Date
2013-10-10
Authors
Sinclair, S Michael
Bhattacharyya, Jayanta
McDaniel, Jonathan R
Gooden, David M
Gopalaswamy, Ramesh
Chilkoti, Ashutosh
Setton, Lori A
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Abstract
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.
Type
Journal article
Subject
Conjugate
Curcumin
Drug depot
Elastin-like polypeptide
Neuroinflammation
Sustained release
Animals
Anti-Inflammatory Agents
Cell Line, Tumor
Curcumin
Delayed-Action Preparations
Drug Delivery Systems
Elastin
Female
Genetic Engineering
Hot Temperature
Humans
Inflammation
Intervertebral Disc Displacement
Mice
Mice, Inbred C57BL
Peptides
Sciatic Nerve
U937 Cells
Permalink
https://hdl.handle.net/10161/7787
Published Version (Please cite this version)
10.1016/j.jconrel.2013.06.032
Publication Info
Sinclair, S Michael; Bhattacharyya, Jayanta; McDaniel, Jonathan R; Gooden, David M; Gopalaswamy, Ramesh; Chilkoti, Ashutosh; & Setton, Lori A (2013). A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation. J Control Release, 171(1). pp. 38-47. 10.1016/j.jconrel.2013.06.032. Retrieved from https://hdl.handle.net/10161/7787.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Chilkoti

Ashutosh Chilkoti

Alan L. Kaganov Distinguished Professor of Biomedical Engineering
Ashutosh Chilkoti is the Alan L. Kaganov Professor of Biomedical Engineering and Chair of the Department of Biomedical Engineering at Duke University. My research in biomolecular engineering and biointerface science focuses on the development of new molecular tools and technologies that borrow from molecular biology, protein engineering, polymer chemistry and surface science that we then exploit for the development of applications that span the range from bioseparations, plasmonic bio
Gooden

David Gooden

Research Scientist

Lori A. Setton

Adjunct Professor of Biomedical Engineering
Research in Setton's laboratory is focused on the role of mechanical factors in the degeneration and repair of soft tissues of the musculoskeletal system, including the intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused on engineering and evaluating materials for tissue regeneration and drug delivery. Studies combining engineering and biology are also used to determine the role of mechanical factors to promote and control healing of cartilaginous tissues. Re
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