Supercritical CO2 (SC-CO2)-assisted electrospray has been successfully performed to obtain a sustained release of ceftriaxone sodium (CFX) from polylactic acid (PLA) nanoparticles. PLA nanoparticles ranged from 270 ± 70 to 310 ± 80 nm, when produced at 140 bar. CFX release in a phosphate-buffered solution ranged from about 5 min, when the pure antibiotic was tested, to a maximum of 1200 min when 140 bar and 4 wt% of PLA + CFX nanoparticles was used: operating at these process conditions, an increase of 240 times of the release time was observed and no interactions were produced between PLA and the antibiotic. The release curves were explained hypothesizing a two-step mass transfer mechanism consisting of polymer swelling and PLA ester bond cleavage
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