Title:
Self-assembling polymeric nanoparticles for enhanced intra-articular anti-inflammatory protein delivery

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dc.contributor.advisor García, Andrés J.
dc.contributor.author Whitmire, Rachel Elisabeth en_US
dc.contributor.committeeMember Babensee, Julia
dc.contributor.committeeMember Levenston, Marc
dc.contributor.committeeMember Lyon, L. Anew
dc.contributor.committeeMember McCarty, Nael
dc.contributor.committeeMember Murthy, Niren
dc.contributor.department Mechanical Engineering en_US
dc.date.accessioned 2012-06-06T16:42:55Z
dc.date.available 2012-06-06T16:42:55Z
dc.date.issued 2012-01-17 en_US
dc.description.abstract The goal of this thesis was to develop a new drug-delivering material to deliver anti-inflammatory protein for treating OA. Our central hypothesis for this work is that a controlled release/presentation system will more effectively deliver anti-inflammatory protein therapies to the OA joint. The primary goal of this work was to synthesize a block copolymer that could self-assemble into injectable, sub-micron-scale particles and would allow an anti-inflammatory protein, IL-1ra, to be tethered to its surface for efficient protein delivery. The block copolymer incorporated an oligo-ethylene monomer for tissue compatibility and non-fouling behavior, a 4-nitrophenol group for efficient protein tethering, and cyclohexyl methacrylate, a hydrophobic monomer, for particle stability. We engineered the copolymer and tested it in both in vitro culture experiments and an in vivo model to evaluate protein retention in the knee joint. The rationale for this project was that the rational design and synthesis of a new drug- and protein-delivering material can create a modular polymer particle that can deliver multi-faceted therapies to treat OA. This work characterizes the in vitro and in vivo behavior of our polymer particle system. The protein tethering strategy allows IL-1ra protein to be tethered to the surface of these particles. Once tethered, IL-1ra maintains its bioactivity and actively targets synoviocytes, cells crucial to the OA pathology. This binding happens in an IL-1-dependent manner. Furthermore, IL-1ra-tethered particles are able to inhibit IL-1beta-induced NF-kappaB activation. These studies show that this particle system has the potential to deliver IL-1ra to arthritic joints and that it has potential for localizing/targeting drugs to inflammatory cells of interest as a new way to target OA drug treatments. en_US
dc.description.degree PhD en_US
dc.identifier.uri http://hdl.handle.net/1853/43587
dc.publisher Georgia Institute of Technology en_US
dc.subject IL-1ra en_US
dc.subject Rats en_US
dc.subject Biomaterials en_US
dc.subject Osteoarthritis en_US
dc.subject.lcsh Polymeric drug delivery system
dc.subject.lcsh Nanoparticles
dc.subject.lcsh Self-assembly (Chemistry)
dc.subject.lcsh Osteoarthritis
dc.subject.lcsh Anti-inflammatory agents
dc.title Self-assembling polymeric nanoparticles for enhanced intra-articular anti-inflammatory protein delivery en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor García, Andrés J.
local.contributor.corporatename George W. Woodruff School of Mechanical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 6236e450-228b-4532-8b5e-812316ac90f3
relation.isOrgUnitOfPublication c01ff908-c25f-439b-bf10-a074ed886bb7
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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