TABLE II.

Summary of recent studies on the production of liposomes and EVs for drug delivery applications using microfluidic platforms. AO: acridine orange hydrochloride; AT: atenolol; BSA: bovine serum albumin; CBD: cannabidiol; Chol: cholesterol; CoQ₁₀: coenzyme Q10; DC: 3β-[N-(dimethylaminoethane)-carbamoyl]; DCP: dihexadecylphosphate; DiO: cell-labeling solution; DMG-PEG2000: 1,2-dimyristoyl-sn-glycerol, methoxy polyethylene glycol 2000; DMPC: 1,2-dimyristoyl-sn-glycero-3-phosphocholine; DOPC: 1,2-dioleoyl- sn-glycero-3-phosphocholine; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DOPS: 1,2-dioleoyl-sn-glycero-3-phospho-L-serine; DOX: doxorubicin; DPPC: 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine; DSPC: 1,2-disteroyl-sn-glycero-3-phosphocholine; DSPE-PEG2000-Folate: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000]; ES: embryonic stem; EV: extracellular vesicles; FA: folic acid; HFF: hydrodynamic flow focusing; iLiNP: invasive lipid nanoparticle production; MEFs: mouse embryonic fibroblasts; NPs: nanoparticles; NV: nanovesicles; PC: phosphatidylcholine; PEG: polyethylene glycol; PEG2000-PE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000; PEG5000-PE: 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; PLGA: poly(lactic-co-glycolic acid); POPC: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; Q: quinine; RhB: rhodamine B; SM: sphingomyelin; SPC: phospholipon 90-G (soybean lecithin, phosphatidylcholine); TAT: cell penetrating peptide; YSK05: pH-sensitive cationic lipid; ZIF-8: zeolitic imidazolate framework-8.

	Microfluidic technique	Size (nm)	Loading capacity	Lipid composition/EV and NV parent cells	Modification\cargos	Throughput	References
Liposomes	HFF	80–110	N.A.	DMPC/Chol/DCP/PEG5000-PE/PEG2000-PE/DSPE-PEG2000-Folate	PEG- and folate- conjugated	N.A.	Hood et al. (2013)
	HFF	190	70%	DMPC/Chol/PEG2000-PE	DOX and AO	1010–1012 liposomes ml−1	Hood et al. (2014)
	HFF	107	75%	DC-Chol/PC/DSPE-PEG	Antisense Bcl-2	N.A.	Koh et al. (2010)
	HFF	70	62%–74%	DMPC/Chol/DSPE-PEG2000	FA and TAT	N.A.	Ran et al. (2018)
	HFF	80–120	N.A.	DMPC/Cholesterol/PEG2000-PE	N.A.	∼ 100 mg h−1	Hood and Devoe, (2015)
	HFF	150	N.A.	N.A.	N.A.	1 kg day−1	Romanowsky et al. (2012)
	T-mixers	<150	∼80%	SPC/Chol	CBD	N.A.	Tiboni et al. (2021)
	SHM	20–140	∼100%	POPC/Chol	DOX	N.A.	Zhigaltsev et al. (2012)
	SHM	40–50	50 mol%	PC/Chol	Propofol	N.A.	Kastner et al. (2015)
	SHM	50–100	20%–40%	PC, DMPC, DPPC, DSPC/Chol	Metformin and glipizide	N.A.	Joshi et al. (2016)
	SHM	70–200	70%–100%	DMPC/DSPC/Chol	AT and Q	N.A.	Guimarães Sá Correia et al. (2017)
	SHM	94–118	90%	DPPC/DSPC/DOPC/Chol	Leukocytes-derived membrane proteins	N.A.	Molinaro et al. (2018)
	SHM	120	17wt. %	DMPC/DPPC/DSPC	Curcumin	N.A.	Hamano et al. (2019)
	SHM	60–100	20%–35%	DMPC:Chol	Proteins	N.A.	Forbes et al. (2019)
	iLiNP	20–100	>90%	YSK05/Chol/DMG-PEG2000	FVII siRNA	N.A.	Kimura et al. (2018)
	iLiNP	50	∼70%	DOPE/SM/DMG-PEG2000	CoQ10	400 μl 0.8 min−1	Hibino et al. (2019)
EVs/EVs-mimetics	Extrusion	60–120	20%	Murine ES cells	EVs-derived mRNAs and proteins	N.A.	Jo et al. (2014)
	Extrusion	100–300	30%	Murine ES cells	Fluorescent beads	∼150 × 108 EVs per 106 cells	Yoon et al. (2015)
	Surface Engineering	50–200	N.A.	Leukocytes	Tumor antigenic peptides	∼2 h for processing 4 104 seeded cells	Zhao et al. (2019)
	Sonication	177.4	91%	Human lung cancer cells A549	EVs membrane-coated PLGA NPs loaded with DiO	N.A.	Liu et al. (2019)
	Sonication	116.2	N.A.	Human lung cancer cells A549	EVs membrane-coated ZIF-8 NPs loaded with FITC-BSA and RhB	N.A.	Lv et al. (2021)
	Electroporation	70–110	2–10 mRNA copies per EV	MEFs	Therapeutic mRNAs	1012 EVs per 106 cells 2–3 day−1	Yang et al. (2020)
	Nanoporation	170 nm	4.9 μg per 108 EVs	Human lung cancer cells A549	DOX	8.5 108 EVs ml−1 at 8 μl min−1	Hao et al. (2021)
	iLiNP	90–121	>50%	DOPC/SM/Chol/DOPS/DOPE	siRNA	N.A.	Kimura et al. (2021)