Nanoprecipitation and nanoformulation of polymers: from history to powerful possibilities beyond poly(lactic acid)

Schubert, Stephanie; Delaney, Joseph T.; Schubert, Ulrich S.

doi:10.1039/c0sm00862a

Cited by 331 publications

(290 citation statements)

References 80 publications

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“…In a tertiary system of ethanol-oilwater such as ours, surface nanodroplets may nucleate on the surface, or through the standard "ouzo effect," namely nucleate in the bulk liquid (13,17,(24)(25)(26), and only later adsorb onto the surface. To find out which of the two processes is dominant, we analyzed the droplet volume and the surrounding dropletdepleted zone, following the modified Voronoi tessellation method in our previous work (27).…”

Section: Resultsmentioning

confidence: 99%

Formation of surface nanodroplets under controlled flow conditions

Zhang

Tan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

128

318

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Nanodroplets on a solid surface (i.e., surface nanodroplets) have practical implications for high-throughput chemical and biological analysis, lubrications, laboratory-on-chip devices, and near-field imaging techniques. Oil nanodroplets can be produced on a solidliquid interface in a simple step of solvent exchange in which a good solvent of oil is displaced by a poor solvent. In this work, we experimentally and theoretically investigate the formation of nanodroplets by the solvent exchange process under well-controlled flow conditions. We find significant effects from the flow rate and the flow geometry on the droplet size. We develop a theoretical framework to account for these effects. The main idea is that the droplet nuclei are exposed to an oil oversaturation pulse during the exchange process. The analysis shows that the volume of the nanodroplets increases with the Peclet number Pe of the flow as ∝ Pe 3=4 , which is in good agreement with our experimental results. In addition, at fixed flow rate and thus fixed Peclet number, larger and less homogeneously distributed droplets formed at less-narrow channels, due to convection effects originating from the density difference between the two solutions of the solvent exchange. The understanding from this work provides valuable guidelines for producing surface nanodroplets with desired sizes by controlling the flow conditions. N anoscale droplets on a substrate (1) are an essential element for a wide range of applications, namely laboratory-on-chip devices, simple and highly efficient miniaturized reactors for concentrating products, high-throughput single-bacteria or singlebiomolecular analysis, encapsulation, and high-resolution imaging techniques, among others (2-5). These droplets are of great interest also because they can have a payload and can flow internally in response to external flow. As a consequence, such droplets are widely exploited in formulation industries. Quite some effort has been devoted to produce a large amount of nanodroplets in a controlled way. The current techniques include trapping by microcavities, emulsion direct adsorption, microprinting, and others (6). The solvent exchange process is a simple and generic approach for producing droplets or bubbles at solid-liquid interfaces that are only several tens to hundreds of nanometers in height, or a few femtoliters in volume (7-11). The approach has attractive advantages, such as its capability of producing a large number of nanodroplets in one simple step, and its generality in chemical composition of the droplet liquid, and flexibility in aspect ratio of the droplets and spatial structure or size of the substrate (9, 12).For the formation of surface nanodroplets by solvent exchange, a hydrophobic substrate is exposed sequentially to two miscible solutions of oil, where the second solvent has a lower solubility of oil than the first. Such solubility difference leads to supersaturation of the liquid with oil during the solvent exchange and consequently to the nucleation of nanodroplets on...

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Section: Resultsmentioning

confidence: 99%

Formation of surface nanodroplets under controlled flow conditions

Zhang

Tan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

128

318

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“…The nanoparticle assembly is governed by the same mechanisms (i.e. nanoprecipitation) for the bulk and microfluidic methods: a solution of polymers in a water miscible organic solvent is mixed with a non-solvent of the polymers (generally water) 33,34,44,45 . The PEG-PLGA block copolymers self-assemble into nanoparticles when they experience a change from organic to aqueous solvent 45 .…”

Section: Introductionmentioning

confidence: 99%

“…Solvent displacement, also referred as nanoprecipitation, is a conventional bulk production technique that has been widely used to manufacture PLGA-based nanoparticles 31,33 . In this method, the polymers are dissolved in a water-miscible organic solvent, which is added dropwise to water under stirring 33,34 .…”

Section: Introductionmentioning

confidence: 99%

“…In this method, the polymers are dissolved in a water-miscible organic solvent, which is added dropwise to water under stirring 33,34 . As a result, there is an inhomogeneous mixing of the organic and aqueous solvents due to the turbulence caused by magnetic stirring 35 and the incorporation of small volumes of polymer solution to a greater volume of water 34 .…”

Section: Introductionmentioning

confidence: 99%

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Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device

et al. 2017

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This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (PEG5K-PLGA55K) matrix. The influence of PEG5K-PLGA55K and conjugated polymers cyanosubstituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (~70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (~70-100 nm) with similar optical properties (quantum yields ~35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG5K-PLGA55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flowbased device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

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“…It is performed by the dropwise addition of an organic solution into an aqueous phase (Lepeltier et al 2014 andSchubert et al 2011). Mixing driven by diffusion over macroscopic length scales is normally very slow, but it can be enhanced by introducing turbulence.…”

Section: Resultsmentioning

confidence: 99%

Fundamental studies on throughput capacities of hydrodynamic flow-focusing microfluidics for producing monodisperse polymer nanoparticles

Baby

Liu

Middelberg

et al. 2017

Chemical Engineering Science

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Microfluidics enables the manipulation of liquids at the picoliter (or less) scale and proves to be superior over conventional bulk methods for mixing and reaction. The ability of microfluidic systems to rapidly mix reagents to provide homogeneous reaction environments, to vary the reaction conditions continuously, and to even allow reagent addition during the progress of a reaction, makes it attractive for nanoparticle synthesis. However, the low production rate limits its practical applications. Different approaches have been developed to achieve higher yield but most of them rely on the design of complex devices. Herein, we investigated fundamentally the throughput capacities of hydrodynamic flow-focusing microfluidics for producing poly (lactide-co-glycolide)-b-polyethylene glycol (PLGA-PEG) nanoparticles with uniform size ranging from 50-150 nm. The effects of different factors of microfluidic design, including channel width, channel depth, channel structure and flow rate ratios, on particle size, size distribution, and production throughput were studied and compared. In contrast to the widely used microfluidic device which has a production rate of 1.8 mg/h, our simple approach is capable of increasing the production rate of nanoparticles by more than two orders of magnitude up to 288 mg/h using a single simple device. This study demonstrated the potentials of using simple 2D microfluidic devices for a large scale production of polymeric nanoparticles that could eliminate the need for designing and fabricating complex microfluidic devices.

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Nanoprecipitation and nanoformulation of polymers: from history to powerful possibilities beyond poly(lactic acid)

Cited by 331 publications

References 80 publications

Formation of surface nanodroplets under controlled flow conditions

Formation of surface nanodroplets under controlled flow conditions

Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device

Fundamental studies on throughput capacities of hydrodynamic flow-focusing microfluidics for producing monodisperse polymer nanoparticles

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