PMID- 22922428 OWN - NLM STAT- MEDLINE DCOM- 20130510 LR - 20181202 IS - 1873-3441 (Electronic) IS - 0939-6411 (Linking) VI - 82 IP - 3 DP - 2012 Nov TI - PLGA microspheres encapsulating siRNA anti-TNFalpha: efficient RNAi-mediated treatment of arthritic joints. PG - 457-64 LID - S0939-6411(12)00248-2 [pii] LID - 10.1016/j.ejpb.2012.07.021 [doi] AB - The aim of this study was to investigate potentialities of poly(dl-lactide-co-glycolide) (PLGA) microspheres for the delivery of small interfering RNAs (siRNAs) against tumor necrosis factor alpha (TNF-alpha) to achieve prolonged and efficient inhibition of TNF-alpha for the treatment of rheumatoid arthritis (RA). PLGA microspheres were prepared by a modified multiple emulsion-solvent evaporation method. The formulations were characterized in terms of morphology, mean diameter and siRNAs distribution, encapsulation efficiency, and in vitro release kinetics. The efficiency of this system was then evaluated both in vitro and in vivo using the murine monocytic cell line J774 and a pre-clinical model of RA, respectively. siRNA-encapsulating PLGA microspheres were characterized by a high encapsulation efficiency and a slow and prolonged anti-TNF-alpha siRNAs. Our results provide evidence that, upon intra-articular administration, PLGA microspheres slowly releasing siRNAs effectively inhibited the expression of TNF-alpha in arthritic joints. Our system might represent an alternative strategy for the design of novel anti-rheumatic therapies based on the use of RNA interference in RA. CI - Copyright (c) 2012 Elsevier B.V. All rights reserved. FAU - Presumey, J AU - Presumey J AD - Inserm, U 844, INM, Hopital Saint Eloi, Montpellier, France. FAU - Salzano, G AU - Salzano G FAU - Courties, G AU - Courties G FAU - Shires, M AU - Shires M FAU - Ponchel, F AU - Ponchel F FAU - Jorgensen, C AU - Jorgensen C FAU - Apparailly, F AU - Apparailly F FAU - De Rosa, G AU - De Rosa G LA - eng PT - Journal Article DEP - 20120816 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) SB - IM MH - Animals MH - Arthritis, Experimental/*pathology/therapy MH - Arthritis, Rheumatoid/*pathology/therapy MH - Cell Line MH - Drug Design MH - Lactic Acid/chemistry MH - Mice MH - Mice, Inbred DBA MH - Microspheres MH - Particle Size MH - Polyglycolic Acid/chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - RNA Interference MH - RNA, Small Interfering/*administration & dosage MH - Time Factors MH - Tumor Necrosis Factor-alpha/*genetics EDAT- 2012/08/28 06:00 MHDA- 2013/05/11 06:00 CRDT- 2012/08/28 06:00 PHST- 2012/04/10 00:00 [received] PHST- 2012/07/30 00:00 [revised] PHST- 2012/07/31 00:00 [accepted] PHST- 2012/08/28 06:00 [entrez] PHST- 2012/08/28 06:00 [pubmed] PHST- 2013/05/11 06:00 [medline] AID - S0939-6411(12)00248-2 [pii] AID - 10.1016/j.ejpb.2012.07.021 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2012 Nov;82(3):457-64. doi: 10.1016/j.ejpb.2012.07.021. Epub 2012 Aug 16.