PMID- 22580113
OWN - NLM
STAT- MEDLINE
DCOM- 20130108
LR  - 20181201
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 161
IP  - 3
DP  - 2012 Aug 10
TI  - MRI-assessed therapeutic effects of locally administered PLGA nanoparticles 
      loaded with anti-inflammatory siRNA in a murine arthritis model.
PG  - 772-80
LID - 10.1016/j.jconrel.2012.05.004 [doi]
AB  - Rheumatoid arthritis is characterized by systemic inflammation of synovial joints 
      leading to erosion and cartilage destruction. Although efficacious anti-tumor 
      necrosis factor alpha (TNF-alpha) biologic therapies exist, there is an unmet medical 
      need for safe and more efficient treatment regimens for disease remission. We 
      evaluated the anti-inflammatory effects of poly(dl-lactide-co-glycolide acid) 
      (PLGA) nanoparticles loaded with small interfering RNA (siRNA) directed against 
      TNF-alpha in vitro and in vivo. The siRNA-loaded PLGA nanoparticles mediated a 
      dose-dependent TNF-alpha silencing in lipopolysaccharide-activated RAW 264.7 cells in 
      vitro. The severity of collagen antibody-induced arthritis in DBA/1J mice was 
      assessed by paw scoring and compared to the degree of magnetic resonance imaging 
      (MRI)-quantified joint effusion and bone marrow edema. Two intra-articular 
      treatments per joint with nanoparticles loaded with TNF-alpha siRNA (1 mug) resulted 
      in a reduction in disease activity, evident by a significant decrease of the paw 
      scores and joint effusions, as compared to treatment with PLGA nanoparticles 
      loaded with non-specific control siRNA, whereas the degree of bone marrow edema 
      in the tibial and femoral head remained unchanged. When the siRNA dose was 5 or 
      10 mug, there was no difference between the specific and the non-specific siRNA 
      treatment groups. These findings suggest that MRI is a promising method for 
      evaluation of early disease progression and treatment in murine arthritis models. 
      In addition, proper siRNA dosing seems to be important for a positive therapeutic 
      outcome in vivo. However, further studies are needed to fully clarify the 
      mechanism(s) underlying the observed anti-inflammatory effects of the 
      siRNA-loaded nanoparticles.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - te Boekhorst, Bernard C M
AU  - te Boekhorst BC
AD  - Department of Biomedical Engineering, Eindhoven University of Technology, P.O. 
      Box 513, Building W-Hoog 4.11, 5600 MB Eindhoven, The Netherlands. 
      b.teboekhorst@maastrichtuniversity.nl
FAU - Jensen, Linda B
AU  - Jensen LB
FAU - Colombo, Stefano
AU  - Colombo S
FAU - Varkouhi, Amir K
AU  - Varkouhi AK
FAU - Schiffelers, Raymond M
AU  - Schiffelers RM
FAU - Lammers, Twan
AU  - Lammers T
FAU - Storm, Gert
AU  - Storm G
FAU - Nielsen, Hanne M
AU  - Nielsen HM
FAU - Strijkers, Gustav J
AU  - Strijkers GJ
FAU - Foged, Camilla
AU  - Foged C
FAU - Nicolay, Klaas
AU  - Nicolay K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120511
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Drug Carriers)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Quaternary Ammonium Compounds)
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)
RN  - MR86K0XRQP (1,2-dioleoyloxy-3-(trimethylammonium)propane)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/pathology/*therapy
MH  - Arthritis, Rheumatoid/pathology/*therapy
MH  - Bone Marrow/drug effects/pathology
MH  - Cell Line
MH  - Drug Carriers/administration & dosage
MH  - Fatty Acids, Monounsaturated/administration & dosage
MH  - Femur
MH  - Gene Silencing
MH  - Lactic Acid/administration & dosage
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Nanoparticles/*administration & dosage
MH  - Polyglycolic Acid/administration & dosage
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Quaternary Ammonium Compounds/administration & dosage
MH  - RNA, Small Interfering/*administration & dosage
MH  - Tibia
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2012/05/15 06:00
MHDA- 2013/01/09 06:00
CRDT- 2012/05/15 06:00
PHST- 2012/01/20 00:00 [received]
PHST- 2012/04/26 00:00 [revised]
PHST- 2012/05/01 00:00 [accepted]
PHST- 2012/05/15 06:00 [entrez]
PHST- 2012/05/15 06:00 [pubmed]
PHST- 2013/01/09 06:00 [medline]
AID - S0168-3659(12)00332-X [pii]
AID - 10.1016/j.jconrel.2012.05.004 [doi]
PST - ppublish
SO  - J Control Release. 2012 Aug 10;161(3):772-80. doi: 10.1016/j.jconrel.2012.05.004. 
      Epub 2012 May 11.