Pharmaceutical Research

, Volume 28, Issue 6, pp 1370–1384

Controlled Release of Anti-inflammatory siRNA from Biodegradable Polymeric Microparticles Intended for Intra-articular Delivery to the Temporomandibular Joint

  • Paschalia M. Mountziaris
  • David C. Sing
  • Sue Anne Chew
  • Stephanie N. Tzouanas
  • E. Dennis Lehman
  • F. Kurtis Kasper
  • Antonios G. Mikos
Research Paper

DOI: 10.1007/s11095-010-0354-9

Cite this article as:
Mountziaris, P.M., Sing, D.C., Chew, S.A. et al. Pharm Res (2011) 28: 1370. doi:10.1007/s11095-010-0354-9

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 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.

KEY WORDS

intra-articular microparticle polyplex temporomandibular joint 

ABBREVIATIONS

anti-TNF-α siRNA

siRNA targeting TNF-α

DLS

dynamic light scattering

MPs

microparticles

N:P ratio

Nitrogen:Phosphate ratio

PBS

phosphate-buffered saline

PEG

poly(ethylene glycol)

PEI

poly(ethylenimine)

PLA

poly(DL-lactic acid)

PLGA

poly(DL-lactic-co-glycolic acid)

r-PEI

rhodamine-conjugated PEI

siRNA

small interfering RNA

TMJ

temporomandibular joint

TNF-α

tumor necrosis factor-α

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Paschalia M. Mountziaris
    • 1
  • David C. Sing
    • 1
  • Sue Anne Chew
    • 1
  • Stephanie N. Tzouanas
    • 1
  • E. Dennis Lehman
    • 1
  • F. Kurtis Kasper
    • 1
  • Antonios G. Mikos
    • 1
  1. 1.Department of BioengineeringRice UniversityHoustonUSA