PMID- 21184147
OWN - NLM
STAT- MEDLINE
DCOM- 20111005
LR  - 20211020
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Linking)
VI  - 28
IP  - 6
DP  - 2011 Jun
TI  - Controlled release of anti-inflammatory siRNA from biodegradable polymeric 
      microparticles intended for intra-articular delivery to the temporomandibular 
      joint.
PG  - 1370-84
LID - 10.1007/s11095-010-0354-9 [doi]
AB  - 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 28 days. 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 500-1,000 nm 
      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.
FAU - Mountziaris, Paschalia M
AU  - Mountziaris PM
AD  - Department of Bioengineering, Rice University, PO Box 1892, MS 142, Houston, 
      Texas 77251-1892, USA.
FAU - Sing, David C
AU  - Sing DC
FAU - Chew, Sue Anne
AU  - Chew SA
FAU - Tzouanas, Stephanie N
AU  - Tzouanas SN
FAU - Lehman, E Dennis
AU  - Lehman ED
FAU - Kasper, F Kurtis
AU  - Kasper FK
FAU - Mikos, Antonios G
AU  - Mikos AG
LA  - eng
GR  - 5 T32 GM008362-19/GM/NIGMS NIH HHS/United States
GR  - 5 T90 DK070121-04/DK/NIDDK NIH HHS/United States
GR  - R01 DE17441/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20101224
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Emulsions)
RN  - 0 (Imines)
RN  - 0 (Polyethylenes)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (poly(ethylene imine))
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Absorbable Implants
MH  - Anti-Inflammatory Agents/administration & dosage/chemistry
MH  - Chemistry, Pharmaceutical/methods
MH  - Delayed-Action Preparations
MH  - Emulsions
MH  - Hydrogen-Ion Concentration
MH  - Imines/administration & dosage/*chemistry
MH  - Injections, Intra-Articular
MH  - Kinetics
MH  - Lactic Acid/administration & dosage/*chemistry
MH  - *Microspheres
MH  - Osteitis/genetics/*therapy
MH  - Particle Size
MH  - Polyethylenes/administration & dosage/*chemistry
MH  - Polyglycolic Acid/administration & dosage/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - RNA, Small Interfering/administration & dosage/*chemistry
MH  - Temporomandibular Joint
EDAT- 2010/12/25 06:00
MHDA- 2011/10/06 06:00
CRDT- 2010/12/25 06:00
PHST- 2010/11/01 00:00 [received]
PHST- 2010/12/14 00:00 [accepted]
PHST- 2010/12/25 06:00 [entrez]
PHST- 2010/12/25 06:00 [pubmed]
PHST- 2011/10/06 06:00 [medline]
AID - 10.1007/s11095-010-0354-9 [doi]
PST - ppublish
SO  - Pharm Res. 2011 Jun;28(6):1370-84. doi: 10.1007/s11095-010-0354-9. Epub 2010 Dec 
      24.