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.


CONCLUSIONS
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.
Butoescu
Nicoleta
N
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Jordan
Olivier
O
Petri-Fink
Alke
A
Hofmann
Heinrich
H
Doelker
Eric
E
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016503:Drug Delivery Systems; D004655:Emulsions; D004867:Equipment Design; D005290:Ferric Compounds / Q000737:chemistry*; D007270:Injections, Intra-Articular; D008280:Magnetics; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008863:Microspheres; D011108:Polymers / Q000737:chemistry*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D004655:Emulsions; D005290:Ferric Compounds; D011108:Polymers; C000499:ferric oxide; D003907:Dexamethasone; C018038:dexamethasone acetate