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. 2023 Sep 18;4(3):031304. doi: 10.1063/5.0150345

FIG. 1.

FIG. 1.

Microfluidic-based liposome production. (A-a) Schematic of a fully integrated microfluidic device made of PDMS and cellulose for liposome synthesis using HFF, buffer exchange via microdialysis and drug loading and (A-b) photograph of the fabricated device. Reproduced with permission from Hood et al., Lab Chip 14(17), 3359–3367 (2014). Copyright 2014 Royal Society of Chemistry. (B) Liposome formation through nanoprecipitation. (B-a) Schematic of a device. Liposomes form through self-assembly when the lipid solution is met with the aqueous buffer from the adjacent channels. (B-b) Fluorescently labeled liposomes with functional groups (PEG-Lip, FA-Lip, TAT-Lip, and FA-TAT-Lip) produced using an HFF-based device and tested on SKOV3 tumor spheroids; scale bars: 200 μm. (B-c) Flow cytometry results demonstrated an increased uptake by the FA-TAT-Lip of 37% and 98% compared to the single ligand TAT-Lip and FA-Lip, respectively. Reproduced with permission from Ran et al., Eur. J. Pharm. Biopharm. 130, 1–10 (2018). Copyright 2018 Elsevier. (C-a) Liposomal curcumins (Lipo-Cur) were prepared by a microfluidic platform equipped with a staggered herringbone micromixer. Reproduced with permission from Stroock et al., Science 295(5555), 647–651 (2002). Copyright 2002 The American Association for the Advancement of Science. (C-b) Lipo-Cur antitumor activity was evaluated in tumor models in mice with EMT6 murine breast tumor cells inoculated into BALB/c mice. 7 days post tumor inoculation, the mice received an injection of either saline, free cisplatin (CDDP), Lipo-Cur, or combination of CDDP and Lipo-Cur. The combination treatment displayed enhanced effect as demonstrated by tumor growth kinetics. Lipo-Cur had also a protective effect against CDDP-induced kidney toxicity. (C-c) The kidney isolated from BALB/C mice was treated with either saline, Lipo-Cur, CDDP, or combination of Lipo-Cur and CDDP. CDDP induced significant acute tubular necrosis as indicated by the arrows, while the kidney histology was normal in other groups. Reproduced with permission from Hamano et al., Mol. Pharm. 16(9), 3957–3967 (2019). Copyright 2019 American Chemical Society. (D-a) Schematic of the iLiNP device featuring a two-dimensional baffle mixer enabling liposomes production and precise size tuning within a range of 20–100 nm, with intervals as small as 10 nm. (D-b) Computational fluid dynamic simulation of ethanol dilution in the iLiNP device at different flow rates demonstrated that the dilution performance was dramatically accelerated at 500 μl/min, and ethanol was completely diluted within 3 ms. Reproduced with permission from Kimura et al., ACS Omega, 3(5), 5044–5051 (2018). Copyright 2018 American Chemical Society.