Co-encapsulation of dexamethasone 21-acetate and SPIONs into biodegradable polymeric microparticles designed for intra-articular delivery.

OBJECTIVE Intra-articular drug delivery systems still suffer from too short-lasting effects. Magnetic particles retained in the joint using an external magnetic field might prolong the local release of an anti-inflammatory drug. For the purpose, superparamagnetic iron oxide nanoparticles (SPIONs) and dexamethasone 21-acetate (DXM) were co-encapsulated into biodegradable microparticles. METHODS Poly(D,L-lactide-co-glycolide) microparticles embedding both SPIONs and DXM were prepared by a double emulsion technique. The formulation was optimized in two steps, a screening design and a full factorial design, aiming at 10-microm particle diameter and high DXM encapsulation efficacy. RESULTS The most significant parameters were the polymer concentration, the stirring speed during solvent extraction and the extractive volume. Increasing the polymer concentration from 200 to 300 mg ml(-1), both the microparticle mean diameter and the DXM encapsulation efficacy increased up to 12 microm and 90%, respectively. The microparticles could be retained with an external magnet of 0.8 T placed at 3 mm. Faster DXM release was obtained for smaller microparticles. CONCLUSION The experimental set-up offered the tools for tailoring a formulation with magnetic retention properties and DXM release patterns corresponding to the required specifications for intra-articular administration.