Controlled release of anti-inflammatory siRNA from biodegradable polymeric microparticles intended for intra-articular delivery to the temporomandibular joint.

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.

• Authors: Paschalia M Mountziaris, David C Sing, Sue Anne Chew, Stephanie N Tzouanas, E Dennis Lehman, F Kurtis Kasper, Antonios G Mikos
• Journal: Pharmaceutical research (Pharm Res) Vol. 28 Issue 6 Pg. 1370-84 (Jun 2011) ISSN: 1573-904X [Electronic] United States
• PMID: 21184147 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Inflammatory Agents
• Delayed-Action Preparations
• Emulsions
• Imines
• Polyethylenes
• RNA, Small Interfering
• poly(ethylene imine)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid

Topics

• Absorbable Implants
• Anti-Inflammatory Agents (administration & dosage, chemistry)
• Chemistry, Pharmaceutical (methods)
• Delayed-Action Preparations
• Emulsions
• Hydrogen-Ion Concentration
• Imines (administration & dosage, chemistry)
• Injections, Intra-Articular
• Kinetics
• Lactic Acid (administration & dosage, chemistry)
• Microspheres
• Osteitis (genetics, therapy)
• Particle Size
• Polyethylenes (administration & dosage, chemistry)
• Polyglycolic Acid (administration & dosage, chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• RNA, Small Interfering (administration & dosage, chemistry)
• Temporomandibular Joint