Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles

Abstract

Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve. The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP). For this purpose, a 3²factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization. The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug. The optimal nanoparticle formulation using 0.25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized. The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1:1), polyD,L-lactide-co-glycolide (PLGA) 50:50 as polymer and an initial mass of 6.6 mg of methylprednisolone. Nanoparticles size and ζ potential of optimized formulation were respectively around 230 nm and −14 mV. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles. Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h. This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.

Keywords::

• Corticosteroid
• hydrophobic drug encapsulation
• nanoparticles
• PLGA
• optimization