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A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.
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 articleSubject
ConjugateCurcumin
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
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https://hdl.handle.net/10161/7787Published Version (Please cite this version)
10.1016/j.jconrel.2013.06.032Publication 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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Show full item recordScholars@Duke
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
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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