Characterization of Nanoscale Loaded Liposomes Produced by 2D Hydrodynamic Flow Focusing

Abstract

This paper presents the continuous flow formation by two-dimensional (2D) hydrodynamic flow focusing (HFF) of nanosized liposomes in microfluidic systems. The size distribution and concentration of the nanosized liposomes, as well as the polydispersity index (PDI) and zeta potential (ZP) of the liposomal dispersions, were investigated under various flow rate ratios (FRRs) and lipid formulations, by the selective incorporation of either positively charged DDAB (didodecyl-dimethylammonium bromide) or negatively charged DOPG (1,2 dioleoyl-snglycero-3-phosphoglycerol) lipids to the main bilayer DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) constituent. The challenges of encapsulating an FITC (fluorescein isothiocyanate)-labeled LC-TAT peptide (long chain of transactivator of transcription peptide), which plays a direct role in the HIV regulation and transcription, overcame and could be achieved via one-step nanoliposomes synthesis, in order to validate the potential of this device as an all-in-one nanoparticle synthesis and loading platform. Liposomes with sizes ranging between 60 to 800 nm were produced with low polydispersity and high particle throughput from alteration of the flow rate ratio and lipid concentration. We introduced the use of nanoparticle tracking analysis (NTA) to estimate for the first time the throughput of microfluidic synthesized liposomal NPs by measuring quantitatively the concentration of the synthesized particles at the outlet. These measurements showed that stable and unilamellar liposomes are generated at a maximum concentration of 1740 × 10 8 particles/mL in less than 2 min, with higher FRR enabling the most rapid generation of liposomes with similar diameter and significant lower polydispersity index than those obtained by other batch techniques.

An ultra-rapid acoustic micromixer for synthesis of organic nanoparticles

“…The initial concentration of the precursors is often considered as the yield of the nanoparticle generation systems in the absence of an actual direct method for nanoparticle concentration measurement. Amrani et al 15 were among the first to use the nanoparticle tracking analysis (NTA) to measure the concentration of liposomes at the output of an HFF system. Interestingly, the authors showed that not only an increase in precursor concentration does not necessarily translate to an increase in the number of nanoparticles, but also it could reduce the nanoparticle concentration at the output.…”

“…13 Passive mixers, especially HFF mixers, are widely used for nanoparticle synthesis and have shown superior size control and distribution over conventional methods. 3,14,15 However, clogging, dilution, and limited mixing performance can restrict their functionality. 16 In contrast, active mixers use an external source of energy such as electrical, magnetic or acoustic energy and generally present a higher mixing efficiency.…”

Microfluidic Generation of Nanomaterials for Biomedical Applications

“…The diameter of the resultant NPs could be regulated by altering the relative flow rate between the central and sheath solution. In addition, when the reaction is restricted within a focused central flow, the channel wall is isolated from the precursors to avoid clogging, thus the consistent formation of NPs can maintain for a long period …”

“…In addition, when the reaction is restricted within a focused central flow, the channel wall is isolated from the precursors to avoid clogging, thus the consistent formation of NPs can maintain for a long period. [106,107]…”

Ultrashort Peptide Theranostic Nanoparticles by Microfluidic-Assisted Rapid Solvent Exchange

“…[14] Different other nanomaterials have been generated successfully via microfluidic mixing methods, e.g. chitosan, [15] lipids, [16][17][18] and poly(lactic-coglycolic acid) based nanoparticles, [19][20][21] DNA-based nanoparticles, [22,23] theranostic lipoplexes, [24] polysulfone, [25,26] or multiple layer assembly for the synthesis of polymer microcapsules. [27] Reviews on engineering nanoparticles in microfluidic devices for drug delivery applications are available [28][29][30][31][32].…”