Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles

Abstiens, Kathrin; Goepferich, Achim

doi:10.1016/j.jddst.2018.12.009

Cited by 52 publications

(46 citation statements)

References 23 publications

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“…Additionally, impact on mitochondrial activity was measured in MTT assays (see Figure S4, Supplementary Material). As discussed in other work, forming nanoparticles by microfluidics leads to an increased control over the production process which in turn generates decreased hydrodynamic diameters and narrow dispersity [38,42,43]. Loy et al produced well-defined and reproducible polyplexes with controlled surface characteristics with the help of microfluidic a self-assembly based on electrostatic interaction [44].…”

Section: Discussionmentioning

confidence: 99%

“…Loy et al produced well-defined and reproducible polyplexes with controlled surface characteristics with the help of microfluidic a self-assembly based on electrostatic interaction [44]. Therefore, microfluidic manufacturing also provides a promising tool for the controlled formation of micelleplexes as it enables a rapid and tunable mixing of both fluids by inducing chaotic advection of the fluid streams and decreasing the average diffusion distance to homogenize the unmixed polymer and siRNA solutions [42]. The resulting nanocarriers are hence expected to mediate highly efficient cellular internalization [45].…”

Section: Discussionmentioning

confidence: 99%

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Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy

et al. 2020

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Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy

et al. 2020

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“…Application of microfluidic devices for various tasks (Whitesides, 2006) and especially for producing delivery systems (Liu et al, 2017) usually improves quality of products. For example, Abstiens & Goepferich (2019) demonstrated that the continuous production of core-lipid anchor nanoparticles from PLGA and PLA-PEG with microfluidics leads to increased control over the production process which in turn generates nanoparticles with decreased size and polydispersity. Automated production of pDNA PEI polyplexes in T-junctions has been shown by Kasper et al (2011) in our lab.…”

Section: Discussionmentioning

confidence: 99%

A microfluidic approach for sequential assembly of siRNA polyplexes with a defined structure-activity relationship

Loy

Klein

Krzysztoń

et al. 2019

PeerJ Materials Science

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Therapeutic nucleic acids provide versatile treatment options for hereditary or acquired diseases. Ionic complexes with basic polymers are frequently used to facilitate nucleic acid's transport to intracellular target sites. Usually, these polyplexes are prepared manually by mixing two components: polyanionic nucleic acids and polycations. However, parameters such as internal structure, size, polydispersity and surface charge of the complexes sensitively affect pharmaceutical efficiency. Hence a controlled assembly is of paramount importance in order to ensure high product quality. In the current study, we present a microfluidic platform for controlled, sequential formulation of polyplexes. We use oligo-amidoamines (termed "oligomers") with precise molecular weight and defined structure due to their solid phase supported synthesis. The assembly of the polyplexes was performed in a microfluidic chip in two steps employing a design of two successive Y junctions: first, siRNA and core oligomers were assembled into core polyplexes. These core oligomers possess compacting, stabilizing, and endosomal escape mediating motifs. Second, new functional motifs were mixed to the core particles and integrated into the core polyplex. The iterative assembly formed multi-component polyplexes in a highly controlled manner and enabled us to investigate structure-function relationships. We chose nanoparticle shielding polyethylene glycol (PEG) and cell targeting folic acid (termed "PEG-ligands") as functional components. The PEG-ligands were coupled to lipid anchor oligomers via strain promoted azidealkyne click chemistry. The lipid anchors feature four cholanic acids for inserting various PEG-ligands into the core polyplex by non-covalent hydrophobic interactions. These core-lipid anchor-PEG-ligand polyplexes containing folate as cell binding ligand were used to determine the optimal PEG-ligand length for transfecting folate receptor-expressing KB cells in vitro. We found that polyplexes with 20 mol % PEG-ligands (relative to n core oligomer ) showed optimal siRNA mediated gene knock-down when containing defined PEG domains of in sum 24 and 36 ethylene oxide repetitions, 12 EOs each from the lipid anchor and 12 or 24 EOs from the PEG-ligand, respectively. These results confirm that transfection efficiency depends on the linker length and stoichiometry and are consistent with previous findings using core-PEG-ligand polyplexes formed by click modification of How to cite this article Loy DM, Klein PM, Krzysztoń R, Lächelt U, Rädler JO, Wagner E. 2019. A microfluidic approach for sequential assembly of siRNA polyplexes with a defined structure-activity relationship.

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“…As the characteristic mixing time in a microfluidic device is much shorter than in a bulk reactor, the resulting nanoparticles exhibit a narrower size distribution and better batch-to-batch consistency. [92,93] While the lower reagent volumes inherent to microfluidics mean that smaller amounts of nanoparticles can be produced, for biological applications the increased quality of the particles in terms of controlled size, shape and composition can outweigh this disadvantage. A wide range of substances have been used to produce nanoparticles for these applications, including a range of polymers, [94][95][96] multimetallic alloys, [97] ceramics, such as hydroxyapatite, [98] and silica.…”

Section: Production Of Nanomaterials On Chipmentioning

confidence: 99%

Chips for Biomaterials and Biomaterials for Chips: Recent Advances at the Interface between Microfabrication and Biomaterials Research

Guttenplan

Birgani

Giselbrecht

et al. 2021

Adv Healthcare Materials

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In recent years, the use of microfabrication techniques has allowed biomaterials studies which were originally carried out at larger length scales to be miniaturized as so-called "on-chip" experiments. These miniaturized experiments have a range of advantages which have led to an increase in their popularity. A range of biomaterial shapes and compositions are synthesized or manufactured on chip. Moreover, chips are developed to investigate specific aspects of interactions between biomaterials and biological systems. Finally, biomaterials are used in microfabricated devices to replicate the physiological microenvironment in studies using so-called "organ-on-chip," "tissue-on-chip" or "disease-on-chip" models, which can reduce the use of animal models with their inherent high cost and ethical issues, and due to the possible use of human cells can increase the translation of research from lab to clinic. This review gives an overview of recent developments at the interface between microfabrication and biomaterials science, and indicates potential future directions that the field may take. In particular, a trend toward increased scale and automation is apparent, allowing both industrial production of micron-scale biomaterials and high-throughput screening of the interaction of diverse materials libraries with cells and bioengineered tissues and organs.

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Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles

Cited by 52 publications

References 23 publications

Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy

Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy

A microfluidic approach for sequential assembly of siRNA polyplexes with a defined structure-activity relationship

Chips for Biomaterials and Biomaterials for Chips: Recent Advances at the Interface between Microfabrication and Biomaterials Research

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