4.8 Article

Supercritical antisolvent production of biodegradable micro- and nanoparticles for controlled delivery of paclitaxel

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 125, Issue 2, Pages 96-106

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2007.10.002

Keywords

supercritical antisolvent; paclitaxel; PLA; biodegradable nanoparticles; ultrasonication; enhanced mixing

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Paclitaxel and poly (L-Lactic acid) (PLA) were co-precipitated to form micro and submicron particles in a manner similar to that used in the supercritical antisolvent with enhanced mass transfer (SAS-EM) process. As compared with conventional processes, a major advantage of supercritical CO2 as an antisolvent in the SAS-EM process is the effective removal of residual organic solvents. In this work, the organic phase was sprayed into supercritical CO2 (for CO2, Tc=31.1 degrees C, Pc=73.8 bar) from a 500 mu m ID capillary nozzle. Ultrasonic vibration with an amplitude of 0 to 120 pm (from a 3/8 '' tip diameter titanium probe) was employed in the high pressure vessel during the antisolvent process to provide enhanced mixing between the solvent and antisolvent phases. The role and effects of ultrasonication on the properties of the resulting particles were studied. When no ultrasonication was applied, micrometer-sized particles were obtained. When ultrasonication was applied, more uniform particles in the submicron size range were obtained. The size of the particles was found to vary with the ultrasonic vibration amplitude. Encapsulation efficiencies up to 83.5% and controlled release of paclitaxel for more than 30 days were achieved with the particles fabricated in this study. (C) 2007 Elsevier B.V. All rights reserved.

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