Controllable Microfluidic Production of Drug-Loaded PLGA Nanoparticles Using Partially Water-Miscible Mixed Solvent Microdroplets as a Precursor

Jiang, Xu; Zhang, Shusheng; Machado, Anaïs; Lecommandoux, Sébastien; Sandre, Olivier; Gu, Frank; Colin, Annie

doi:10.1038/s41598-017-05184-5

Cited by 96 publications

(92 citation statements)

References 43 publications

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“…Despite these advantages, limitations such as high batch-to-batch variations, non-homogenous reaction environment 27 and insufficient production rate reveal the need to move towards techniques providing a higher control in the production of nanosystems with well-defined features.…”

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confidence: 99%

“…One of the first examples is presented by Karnik and co-workers 43 , who produced PLGA-PEG nanoparticles, studying the effect of the flow-rate ratio on particle size and polydispersity by micellization. Recently, Xu et al, proposed a continuous flow focusing-based strategy to improve the encapsulation efficiency (EE%) of Tamoxifen and Doxorubicin, a hydrophobic and a hydrophilic anticancer drug respectively, in PLGA NPs 27 . In this work, they demonstrated that an improved EE% translates into a more controlled drug release.…”

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confidence: 99%

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A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

Tammaro

Polidoro

Romano

et al. 2020

Sci Rep

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The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. This advancement can be reached through the use of multimodal tracers, and nanotechnology-based solutions allow the simultaneous delivery of different diagnostic compounds moving a step towards their safe administration for multimodal imaging acquisition. Among different processes, nanoprecipitation is a consolidate method for the production of nanoparticles and its implementation in microfluidics can further improve the control over final product features accelerating its potential clinical translation. A Hydrodynamic Flow Focusing (HFF) approach is proposed to produce through a ONE-STEP process Multimodal Pegylated crosslinked Hyaluronic Acid NanoParticles (PEG-cHANPs). A monodisperse population of NPs with an average size of 140 nm is produced and Gd-DTPA and ATTO488 compounds are co-encapsulated, simultaneously. The results showed that the obtained multimodal nanoparticle could work as MRI/Optical imaging probe. Furthermore, under the Hydrodenticity effect, a boosting of the T1 values with respect to free Gd-DTPA is preserved. Multimodal Imaging is a promising approach that allows the combination of different imaging techniques, overcoming limitations proper of every single modality 1,2. For example, recently, Magnetic Resonance Imaging (MRI) and Optical imaging (OI) have been used in combination to obtain the excellent sensitivity of the OI with the high spatial resolution of the MRI 3-5. Image acquisition can occur at different times (asynchronously) requiring post-processing analyses performed through digital image manipulation techniques; however, the best consistency both in time and space is achieved when images are simultaneously acquired (synchronously) 6. Despite the great advantages in the Hardware developments, probes able to support simultaneous acquisitions are still missing. Indeed, in current clinical practice, a cocktail of diagnostic compounds is injected with extremely high risk for the patient. In this scenario, the possibility to efficiently co-deliver through a single vector, different diagnostic compounds for different imaging modalities represents a key point. This challenge can be adequately tackled by applying nanotechnologies to the medical field 7-9. Indeed, nanosystems can be used as vectors of active agents and their composition, size, shape, and surface chemistry can be finely modulated to obtain the simultaneous delivery of multiple diagnostic compounds with a significant impact on an early and accurate diagnosis 10-12. Nanovectors can provide simultaneous visualization of the diseased site through different innovative imaging techniques, enhanced-circulation time for the diagnostic compounds, controlled release kinetics, and superior dose scheduling for improved patient compliance 13. However, when systemically injected, nanoparticles are immediately sequestered by macrophages

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confidence: 99%

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confidence: 99%

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

Tammaro

Polidoro

Romano

et al. 2020

Sci Rep

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“…A continuous microfluidic flow-focusing method has also been engineered, providing a rapid, efficient, and low-cost formulation of hydrophobic molecules (e.g. tamoxifen) with high encapsulation efficiency [15]. Moreover, microfluidic systems have also been used for the formulation of nanoparticles (e.g.…”

Section: Microfluidicsmentioning

confidence: 99%

How innovative drug delivery devices can help realize clinical utility of new effective therapies

Lamprou

Singh

Larrañeta

et al. 2019

Expert Opinion on Drug Delivery

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“…Droplet microfluidics involves sample partitioning into nanoliter or smaller volumes and has been extensively used in a variety of fields including biology, medicine, chemistry and physics [1][2][3][4]. Most commonly, aqueous fluids are encapsulated into droplets surrounded by a continuous phase of an oil surfactant mixture.…”

Section: Introductionmentioning

confidence: 99%

High-throughput magnetic particle washing in nanoliter droplets using serial injection and splitting

Stephenson

2018

Micro and Nano Syst Lett

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Droplet microfluidics has emerged as a promising technique to perform high-throughput, massively-parallel chemical and molecular biological reactions. Droplet microfluidic operations such as droplet generation, sorting, and fluid addition are well established; however, fluid exchange (i.e. washing) at high-throughput is challenging to implement. Here we present a microfluidic device architecture that utilizes wash buffer injection preceding a splitting junction in proximity to a magnetic field to transfer paramagnetic microparticles across a concentration gradient within a single droplet. The device can operate at high throughput (50 Hz) while preserving input droplet volume at the collection outlet as verified using high speed imaging. Using a two-stage device, combined microparticle retention rates (up to 97.5%) and high wash efficiency (92.9%) is demonstrated using dye absorbance and fluorescence. This method can be performed in a serial array to obtain an arbitrary degree of wash efficiency and integrated into lab-on-a-chip systems for use in multi-step microfluidic bioassays or single-cell genomic applications requiring high-fidelity washing steps within droplets. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Controllable Microfluidic Production of Drug-Loaded PLGA Nanoparticles Using Partially Water-Miscible Mixed Solvent Microdroplets as a Precursor

Cited by 96 publications

References 43 publications

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

How innovative drug delivery devices can help realize clinical utility of new effective therapies

High-throughput magnetic particle washing in nanoliter droplets using serial injection and splitting

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