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Microfluidic Assembly of pDNA/Cationic Liposome Lipoplexes with High pDNA Loading for Gene Delivery

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School of Chemical Engineering, University of Campinas, UNICAMP, Campinas, SP 13083-970, Brazil
Brazilian Synchrotron Light Laboratory, CNPEM, Campinas, São Paulo 13083-100, Brazil
§ Institute of Physics, University of São Paulo, USP, São Paulo, SP 05508, Brazil
Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, SP 13083-970, Brazil
*E-mail: latorre@feq unicamp.br. Telephone: +55 19 35210397. Fax: +55 19 35213910.
Cite this: Langmuir 2016, 32, 7, 1799–1807
Publication Date (Web):January 27, 2016
https://doi.org/10.1021/acs.langmuir.5b04177
Copyright © 2016 American Chemical Society

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    Abstract

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    Microfluidics offers unique characteristics to control the mixing of liquids under laminar flow. Its use for the assembly of lipoplexes represents an attractive alternative for the translation of gene delivery studies into clinical trials on a sufficient throughput scale. Here, it was shown that the microfluidic assembly of pDNA/cationic liposome (CL) lipoplexes allows the formation of nanocarriers with enhanced transfection efficiencies compared with the conventional bulk-mixing (BM) process under high pDNA loading conditions. Lipoplexes generated by microfluidic devices exhibit smaller and more homogeneous structures at a molar charge ratio (R±) of 1.5, representing the ratio of lipid to pDNA content. Using an optimized model to fit small-angle X-ray scattering (SAXS) curves, it was observed that large amounts of pDNA induces the formation of aggregates with a higher number of stacked bilayers (N ∼ 5) when the BM process was used, whereas microfluidic lipoplexes presented smaller structures with a lower number of stacked bilayers (N ∼ 2.5). In vitro studies further confirmed that microfluidic lipoplexes achieved higher in vitro transfection efficiencies in prostate cancer cells at R ± 1.5, employing a reduced amount of cationic lipid. The correlation of mesoscopic characteristics with in vitro performance provides insights for the elucidation of the colloidal arrangement and biological behavior of pDNA/CL lipoplexes obtained by different processes, highlighting the feasibility of applying microfluidics to gene delivery.

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