Preparation and characterisation of Poly (D,L-lactic-co-glycolic acid) microspheres containing desferrioxamine

Abstract

The iron chelator desferrioxamine (DFO) demonstrates antimalarial activity upon multiple or continuous parenteral administration. The aim of this study was to develop a controlled release system for the water-soluble drug DFO based on poly (D,L-lactic-co-glycolic acid) (PLGA). PLGA microspheres containing DFO were prepared using the water-in-oil-in-water (w/o/w) solvent evaporation technique. The influence of formulation parameters (internal phase volume and polymer concentration) on the microsphere characteristics (particle size, porosity, encapsulation efficiency of DFO) and DFO release profile were investigated. An increasing internal phase volume at a fixed polymer concentration resulted in an increasing volume weight mean diameter, an increasing porosity and a decreasing encapsulation efficiency. An increasing PLGA concentration at a fixed internal phase volume resulted in a decreasing porosity of the particles with an increased volume weight mean diameter and encapsulation efficiency of DFO. DFO was released from the microspheres in an initial burst (controlled by formulation parameters) followed by marginal release and a pulse release at the time the microspheres start to dissolve (20-30 days). The release of DFO was incomplete after complete dissolution of the microspheres. This is probably caused by the instability of DFO at low pH, generated upon degradation of the PLGA matrix.