Study of Fe3O4–PLLA–PEG–PLLA magnetic microspheres based on supercritical CO2: Preparation, physicochemical characterization, and drug loading investigation

Abstract

The Fe3O4–poly(l-lactide)–poly(ethylene glycol)–poly(l-lactide) magnetic microspheres (Fe3O4–PLLA–PEG–PLLA MMPs) were successfully developed in a process of suspension-enhanced dispersion by supercritical CO2 (SpEDS), and their physicochemical properties were characterized. Methotrexate (MTX)-loaded Fe3O4–PLLA–PEG–PLLA MMPs were produced by co-precipitation and microencapsulation processes, and their drug loads, encapsulation efficiencies and drug release profiles were investigated. The resulting Fe3O4–PLLA–PEG–PLLA MMPs have a spherical shape, with a good magnetic response, which is dominated by the Fe3O4 content. With an increase in the Fe3O4 nanoparticle content (5.6%, 13.2%, 19.6%, 23.7%, and 42.8%), the particle size of the resulting MMPs decreased (mean diameters: 666, 629, 583, 578, and 566nm, respectively); their corresponding saturation magnetizations increased dramatically (5.0, 16.3, 35.6, 3.1×103, and 1.3×105emu/g, respectively). Compared with the parallel study of co-precipitation, the microencapsulation process produced MTX-loaded MMPs with a smaller mean particle size (564nm versus 677nm), a higher drug load (8.9% versus 7.2%), a higher encapsulation efficiency (60.8% versus 29.4%), and a much longer sustained-release effect without a burst release (12.6% in 0.5h and 98.9% in 144h versus 52.8% in 0.5h and 96.1% in 6h). The results also indicate that the SpEDS process is a physical process to produce a magnetic drug carrier, with a very low organic solvent residue of 20ppm, which would have potential as a sustained and targeted drug delivery system when combined with the microencapsulation process.