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Preparation of methotrexate-loaded, large, highly-porous PLLA microspheres by a high-voltage electrostatic antisolvent process

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Abstract

A high-voltage (10 kV) electrostatic antisolvent process was used to prepare methotrexate (MTX)-loaded, large, highly-porous poly-l-lactide (PLLA) microspheres. MTX solution in dimethyl sulfoxide (DMSO) and PLLA solution in dichloromethane (DCM) were homogeneously mixed, and then ammonium bicarbonate (AB) aqueous solution was added. The mixed solution was emulsified by ultrasonication with Pluronic F127 (PF127) as an emulsion stabilizer. The emulsion was electrosprayed by the specific high-voltage apparatus and dropped into a 100 mL of ethanol, which acted as an antisolvent for the solute and extracted DMSO and DCM, causing the co-precipitation of PLLA and MTX, thus forming microspheres with AB aqueous micro-droplets uniformly inlaid. The obtained MTX–PLLA microspheres were subsequently lyophilized to obtain large, highly-porous MTX–PLLA microspheres, which exhibited an identifiable spherical shape and a rough surface furnished with open pores, with a mean particle size of 25.0 μm, mass median aerodynamic diameter of 3.1 ± 0.2 μm, fine-particle fraction of 57.1 ± 1.6 %, and porosity of 81.8 %; furthermore, they offered a sustained release of MTX. X-ray diffraction and Fourier transform-infrared spectra revealed that no crystallinity or alteration of chemical structure occurred during the high-voltage electrostatic antisolvent process, which in this study was proved to have great potential for preparing highly-porous drug-loaded polymer microspheres for use in pulmonary drug delivery.

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Acknowledgments

Financial supports from Natural Science Foundation of Fujian Province (2010J05027 and 2011J01223) and National Natural Science Foundation of China (51103049, 81171471 and 31170939) are gratefully acknowledged.

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Authors and Affiliations

  1. College of Chemical Engineering, Huaqiao University, Xiamen, 361021, China

    Ai-Zheng Chen, Yue-Mei Yang, Shi-Bin Wang, Guang-Ya Wang, Yuan-Gang Liu & Qing-Qing Sun

  2. Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen, 361021, China

    Ai-Zheng Chen, Shi-Bin Wang & Yuan-Gang Liu

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  1. Ai-Zheng Chen
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  2. Yue-Mei Yang
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  3. Shi-Bin Wang
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  4. Guang-Ya Wang
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Correspondence to Ai-Zheng Chen or Shi-Bin Wang.

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Chen, AZ., Yang, YM., Wang, SB. et al. Preparation of methotrexate-loaded, large, highly-porous PLLA microspheres by a high-voltage electrostatic antisolvent process. J Mater Sci: Mater Med 24, 1917–1925 (2013). https://doi.org/10.1007/s10856-013-4942-1

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  • DOI: https://doi.org/10.1007/s10856-013-4942-1

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