Abstract

The aim of this study was to prepare biodegradable sustained release magnetite microspheres sized between 1 to 2 μm. The microspheres with or without magnetic materials were prepared by a W/O/W double emulsion solvent evaporation technique using poly(lactide-co-glycolide) (PLGA) as the biodegradable matrix forming polymer. Effects of manufacturing and formulation variables on particle size were investigated with non-magnetic microspheres. Microsphere size could be controlled by modification of homogenization speed, PLGA concentration in the oil phase, oil phase volume, solvent composition, and polyvinyl alcohol (PVA) concentration in the outer water phase. Most influential were the agitation velocity and all parameters that influence the kinematic viscosity of oil and outer water phase, specifically the type and concentration of the oil phase. The magnetic component yielding homogeneous magnetic microspheres consisted of magnetite nanoparticles of 8 nm diameter stabilized with a polyethylene glycole/polyacrylic acid (PEG/PAA) coating and a saturation magnetization of 47.8 emu/g. Non-magnetic and magnetic microspheres had very similar size, morphology, and size distribution, as shown by scanning electron microscopy. The optimized conditions yielded microspheres with 13.7 weight% of magnetite and an average diameter of 1.37 μm. Such biodegradable magnetic microspheres seem appropriate for vascular administration followed by magnetic drug targeting.

Highlights

  • Controlled release parenteral nanospheres and microspheres made from biodegradable polymers such as poly (PLGA) have been widely investigated for a variety of therapeutic agents

  • Our experiments showed that the size of biodegradable PLGA microspheres can be controlled by modifying the process and formulation variables, in particular the agitation velocity and the parameters that influence the kinematic viscosity of both the oil phase and outer water phase, such as the type and concentration of the oil phase

  • Using nanomagnetite particles coated with PAA/PEG complied with these conditions and did not seem to change the final microsphere properties at all

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Summary

Introduction

Controlled release parenteral nanospheres and microspheres made from biodegradable polymers such as poly (lactide-co-glycolide) (PLGA) have been widely investigated for a variety of therapeutic agents. PLGA polymers have been used in the preparation of controlled release delivery systems, such as Lupron Depot® (TAP Pharmaceutical Product Inc.), ZoladexTM (Zeneca), DecapeptylTM (Ipsen Biotech), and Prostap SRTM (Lederle), all of which are licensed for intramuscular use in humans in both Europe and the U.S.A. Functionalized magnetic nanospheres and microspheres (MMS) are usually formulated by encapsulation of magnetic nanoparticles (e.g., magnetite) into the biodegradable polymeric matrix and are being used evermore for biomedical applications including drug delivery, diagnostic magnetic resonance imaging (MRI), magnetic cell separation, tissue repair, hyperthermia and magnetofection [4,5,6,7,8].

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