Microfluidic synthesis of dye-loaded polycaprolactone-block-poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery

Bains, Aman; Wulff, Jeremy E.; Moffitt, Matthew G.

doi:10.1016/j.jcis.2016.04.010

Cited by 32 publications

(62 citation statements)

References 68 publications

(122 reference statements)

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“…The restricted volume allows to limit the diffusion distance of solvent and antisolvent, therefore it regulates the mixing of the two liquids that can be further controlled by modification of stream flow rates or chip design [53][54][55][56]. The fine control over this process results in tunability of the NP properties, such as its size, surface characteristics or crystallinity [57][58][59]. It reduces batch-to-batch variability and enables the investigation on how the NPs properties can be tailored upon formulation parameters, what was not possible within the bulk mixing method [45,60,61].…”

Section: Introductionmentioning

confidence: 99%

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

et al. 2021

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Amphiphilic block co-polymer nanoparticles are interesting candidates for drug delivery as a result of their unique properties such as the size, modularity, biocompatibility and drug loading capacity. They can be rapidly formulated in a nanoprecipitation process based on self-assembly, resulting in kinetically locked nanostructures. The control over this step allows us to obtain nanoparticles with tailor-made properties without modification of the co-polymer building blocks. Furthermore, a reproducible and controlled formulation supports better predictability of a batch effectiveness in preclinical tests. Herein, we compared the formulation of PLGA-PEG nanoparticles using the typical manual bulk mixing and a microfluidic chip-assisted nanoprecipitation. The particle size tunability and controllability in a hydrodynamic flow focusing device was demonstrated to be greater than in the manual dropwise addition method. We also analyzed particle size and encapsulation of fluorescent compounds, using the common bulk analysis and advanced microscopy techniques: Transmission Electron Microscopy and Total Internal Reflection Microscopy, to reveal the heterogeneities occurred in the formulated nanoparticles. Finally, we performed in vitro evaluation of obtained NPs using MCF-7 cell line. Our results show how the microfluidic formulation improves the fine control over the resulting nanoparticles, without compromising any appealing property of PLGA nanoparticle. The combination of microfluidic formulation with advanced analysis methods, looking at the single particle level, can improve the understanding of the NP properties, heterogeneities and performance.

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Section: Introductionmentioning

confidence: 99%

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

et al. 2021

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“…The morphologies of amphiphilic block copolymers self-assembled in a gas-liquid microfluidic reactor are entirely different from off-chip equilibrium structures [145]. Moffitt's group has intensively studied the fascinating effects of high-shear environments in segmented gas-liquid microfluidic reactors on the self-assembly of block copolymers (Figure 12a) [146][147][148]. Figure 12d).…”

Section: Structured Nanoparticlesmentioning

confidence: 99%

Current developments and applications of microfluidic technology toward clinical translation of nanomedicines

Liu

Zhang

Fontana

et al. 2018

Advanced Drug Delivery Reviews

166

127

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Nanoparticulate drug delivery systems hold great potential for the therapy of many diseases, especially cancer. However, the translation of nanoparticulate drug delivery systems from academic research to industrial and clinical practice has been slow. This slow translation can be ascribed to the high batch-to-batch variations and insufficient production rate of the conventional preparation methods, and the lack of technologies for rapid screening of nanoparticulate drug delivery systems with high correlation to the in vivo tests. These issues can be addressed by the microfluidic technologies. For example, microfluidics can not only produce nanoparticles in a well-controlled, reproducible, and high-throughput manner, but also create 3D environments with continuous flow to mimic the physiological and/or pathological processes. This review provides an overview of the microfluidic devices developed to prepare nanoparticulate drug delivery systems, including drug nanosuspensions, polymer nanoparticles, polyplexes, structured nanoparticles and theranostic nanoparticles. We also highlight the recent advances of microfluidic systems in fabricating the increasingly realistic models of the in vivo milieu for rapid screening of nanoparticles. Overall, the microfluidic technologies offer a promise approach to accelerate the clinical translation of nanoparticulate drug delivery systems.

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“…Due to the high shear at high flow rates, the copolymer chains self-assembled into spherical nanocomposites instead of into lamellae that are generated at low shear. The specific morphologies, such as spool generated from the shear control, have been employed to manipulate the loading and releasing speeds of drugs and dyes by the group of Matthew G. Moffitt [85,86]. Compared to single-phase microfluidic reactors, the shear force induced by segment movements and internal recirculation is another unique property of compartments for creating various nanomaterial morphologies.…”

Section: Reaction Within Compartments Of Taylor and Bubbly Flowmentioning

confidence: 99%

Segmented Microfluidic Flow Reactors for Nanomaterial Synthesis

Kim

Chang

2020

Nanomaterials

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Microfluidic reactors have remarkably promoted the synthesis and investigation of advanced nanomaterials due to their continuous mode and accelerated heat/mass transfer. Notably, segmented microfluidic flow reactors (SMFRs) are an important class of microfluidic reactors that have been developed to accurately manipulate nanomaterial synthesis by further improvement of the residence time distributions and unique flow behaviors. This review provided a survey of the nanomaterial synthesis in SMFRs for the aspects of fluid dynamics, flow patterns, and mass transfer among and within distinct phases and provided examples of the synthesis of versatile nanomaterials via the use of different flow patterns.

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Microfluidic synthesis of dye-loaded polycaprolactone-block-poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery

Cited by 32 publications

References 68 publications

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

Current developments and applications of microfluidic technology toward clinical translation of nanomedicines

Segmented Microfluidic Flow Reactors for Nanomaterial Synthesis

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