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


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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Publication Info

Sinclair, S Michael, Jayanta Bhattacharyya, Jonathan R McDaniel, David M Gooden, Ramesh Gopalaswamy, Ashutosh Chilkoti and Lori A Setton (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.

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David Gooden

Research Scientist

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 biosensors, low-cost clinical diagnostics, and drug delivery.

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