caa a22 4500 445311843 CHVBK 20180317142632.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s11095-010-0354-9 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0354-9 Controlled Release of Anti-inflammatory siRNA from Biodegradable Polymeric Microparticles Intended for Intra-articular Delivery to the Temporomandibular Joint [Elektronische Daten] [Paschalia Mountziaris, David Sing, Sue Chew, Stephanie Tzouanas, E. Lehman, F. Kasper, Antonios Mikos] ABSTRACT: Purpose: As the next step in the development of an intra-articular controlled release system to treat painful temporomandibular joint (TMJ) inflammation, we developed several biodegradable poly(DL-lactic-co-glycolic acid) (PLGA)-based microparticle (MP) formulations encapsulating a model anti-inflammatory small interfering RNA (siRNA) together with branched poly(ethylenimine) (PEI) as a transfecting agent. The effect of siRNA loading and N:P ratio on the release kinetics of siRNA-PEI polyplexes was determined, and the size and N:P ratio of the polyplexes released over time was characterized. Methods: Polyplex-loaded PLGA MPs were prepared using an established double emulsion technique. Increasing the pH of the release samples enabled siRNA-PEI dissociation and subsequent measurement of the release of each component over 28days. Polyplex diameter was measured for all release samples and compared to freshly prepared siRNA-PEI under simulated physiologic conditions. Results: Systematic variation of siRNA loading and N:P ratio resulted in distinct siRNA and PEI release profiles. Polyplex diameter remained constant despite large variations in the relative amounts of siRNA and PEI. Excess PEI was sequestered through complexation with 500-1,000nm diameter PLGA MP-derived particles, including small MPs and PLGA degradation products. Conclusions: These PLGA MP formulations show exciting potential as the first intra-articular TMJ controlled release system. Springer Science+Business Media, LLC, 2010 intra-articular nationallicence microparticle nationallicence polyplex nationallicence temporomandibular joint nationallicence anti-TNF-α siRNA : siRNA targeting TNF-α nationallicence DLS : dynamic light scattering nationallicence MPs : microparticles nationallicence N:P ratio : Nitrogen:Phosphate ratio nationallicence PBS : phosphate-buffered saline nationallicence PEG : poly(ethylene glycol) nationallicence PEI : poly(ethylenimine) nationallicence PLA : poly(DL-lactic acid) nationallicence PLGA : poly(DL-lactic-co-glycolic acid) nationallicence r-PEI : rhodamine-conjugated PEI nationallicence siRNA : small interfering RNA nationallicence TMJ : temporomandibular joint nationallicence TNF-α : tumor necrosis factor-α nationallicence Mountziaris Paschalia Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Sing David Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Chew Sue Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Tzouanas Stephanie Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Lehman E. Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Kasper F. Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Mikos Antonios Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/6(2011-06-01), 1370-1384 0724-8741 28:6<1370 2011 28 11095 https://doi.org/10.1007/s11095-010-0354-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0354-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mountziaris Paschalia Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 700 1- Sing David Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 700 1- Chew Sue Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 700 1- Tzouanas Stephanie Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 700 1- Lehman E. Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 700 1- Kasper F. Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 700 1- Mikos Antonios Department of Bioengineering, Rice University, P.O. Box1892, MS 142, 77251-1892, Houston, Texas, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/6(2011-06-01), 1370-1384 0724-8741 28:6<1370 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer