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

Abstract

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-μm 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 μm 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.

Key Words: :

• Magnetic microparticles
• dexamethasone
• experimental design
• drug release
• superparamagnetic iron oxide nanoparticles (SPION)