A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Sinclair, SM; Bhattacharyya, J; McDaniel, JR; Gooden, DM; Gopalaswamy, R; Chilkoti, A; Setton, LA
Published Date
- October 2013
Published In
Volume / Issue
- 171 / 1
Start / End Page
- 38 - 47
PubMed ID
- 23830979
Pubmed Central ID
- PMC3990405
Electronic International Standard Serial Number (EISSN)
- 1873-4995
International Standard Serial Number (ISSN)
- 0168-3659
Digital Object Identifier (DOI)
- 10.1016/j.jconrel.2013.06.032
Language
- eng