Fabrication of hydrophilic paclitaxel-loaded PLA-PEG-PLA microparticles via SEDS process

Abstract

In this work, chemically bonded poly(D, L-lactide)-polyethylene glycol-poly(D, L-lactide) (PLA-PEG-PLA) triblock copolymers with various PEG contents and PLA homopolymer were synthesized via melt polymerization, and were confirmed by FTIR and ¹H-NMR results. The molecular weight and polydispersity of the synthesized PLA and PLA-PEG-PLA copolymers were investigated by gel permeation chromatography. Hydrophilicity of the copolymers was identified by contact angle measurement. PLA-PEG-PLA and PLA microparticles loaded with and without PTX were then produced via solution enhanced dispersion by supercritical CO₂ (SEDS) process. The effect of the PEG content on the particle size distribution, morphology, drug load, and encapsulation efficiency of the fabricated microparticles was also studied. Results indicate that PLA and PLA-PEG-PLA microparticles all exhibit sphere-like shape with smooth surface, when PEG content is relatively low. The produced microparticles have narrow particle size distributions and small particle sizes. The drug load and encapsulation efficiency of the produced microparticles decreases with higher PEG content in the copolymer matrix. Moreover, high hydrophilicity is found when PEG is chemically attached to originally hydrophobic PLA, providing the produced drug-loaded microparticles with high hydrophilicity, biocompatibility, and prolonged circulation time, which are considered of vital importance for vessel-circulating drug delivery system.

Keywords

supercritical CO₂ (scCO₂) / SEDS / PLA-PEG-PLA / paclitaxel

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Acknowledgements

Financial support from the National Natural Science Foundation of China (Grant No. 50873066), and the Key Technologies Research and Development Program of Sichuan Province (Grant No. 2006Z08-001-1) is also gratefully acknowledged.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg