Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation

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dc.citation.firstpage3552en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitleActa Biomaterialiaen_US
dc.citation.lastpage3560en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorMountziaris, Paschalia M.en_US
dc.contributor.authorTzouanas, Stephanie N.en_US
dc.contributor.authorSing, David C.en_US
dc.contributor.authorKramer, Phillip R.en_US
dc.contributor.authorKasper, F. Kurtisen_US
dc.contributor.authorMikos, Antonios G.en_US
dc.date.accessioned2015-01-06T15:49:12Zen_US
dc.date.available2015-01-06T15:49:12Zen_US
dc.date.issued2012en_US
dc.description.abstractWe investigated the in vivo therapeutic efficacy of an intra-articular controlled release system consisting of biodegradable poly(dl-lactic-co-glycolic acid) (PLGA) microparticles (MPs) encapsulating anti-inflammatory small interfering RNA (siRNA), together with branched poly(ethylenimine) (PEI) as a transfecting agent, in a rat model of painful temporomandibular joint (TMJ) inflammation. The in vivo effects of PLGA MP dose and siRNA-PEI polyplex delivery were examined via non-invasive meal pattern analysis and by quantifying the protein level of the siRNA target as well as of several downstream inflammatory cytokines. Controlled release of siRNA-PEI from PLGA MPs significantly reduced inflammation-induced changes in meal patterns compared to untreated rats with inflamed TMJs. These changes correlated to decreases in tissue-level protein expression of the siRNA target to 20-50% of the amount present in the corresponding control groups. Similar reductions were also observed in the expression of downstream inflammatory cytokines, e.g. interleukin-6, whose tissue levels in the siRNAﾖPEI PLGA MP groups were 50% of the values for the corresponding controls. This intra-articular sustained release system has significant implications for the treatment of severe TMJ pain, and also has the potential to be readily adapted and applied to mitigate painful, chronic inflammation in a variety of conditions.en_US
dc.identifier.citationMountziaris, Paschalia M., Tzouanas, Stephanie N., Sing, David C., et al.. "Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation." <i>Acta Biomaterialia,</i> 8, no. 10 (2012) Elsevier: 3552-3560. http://dx.doi.org/10.1016/j.actbio.2012.06.031.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.actbio.2012.06.031en_US
dc.identifier.urihttps://hdl.handle.net/1911/78885en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordcontrolled drug releaseen_US
dc.subject.keyworddrug deliveryen_US
dc.subject.keywordmicrosphereen_US
dc.subject.keywordinflammationen_US
dc.subject.keywordimmunomodulationen_US
dc.titleIntra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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