Nanomanufacturing through microfluidic-assisted nanoprecipitation: Advanced analytics and structure-activity relationships

Donno, Roberto; Gennari, Arianna; Lallana, Enrique; rosa, Julio Manuel Ríos De la; d’Arcy, Richard; Treacher, Kevin; Hill, Kathryn J.; Ashford, Marianne; Tirelli, Nicola

doi:10.1016/j.ijpharm.2017.10.006

Cited by 43 publications

(36 citation statements)

References 40 publications

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“…It should be mentioned that the anionic nature that PLGA gives to the nanoparticles also depends on its molecular weight and concentration. 94,95 PVA concentration effects on the z of the PNP Fig. 5C presents the z of PNP obtained with different C PVA for both techniques, emulsication and nanoprecipitation.…”

Section: Plga Concentration Effects On the Z Of The Pnpmentioning

confidence: 99%

PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters

et al. 2020

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Section: Plga Concentration Effects On the Z Of The Pnpmentioning

confidence: 99%

PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters

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“…The nanoprecipitation conditions used herein were analogous to our previously optimized protocol that rendered Pluronic F127/PLGA particles of a desired size, low polydispersity, high stability, good surface coverage and a spherical shape 34 . For the preparation of nanoparticle formulations exposing varying densities of peptide, we used RGD-functionalized and pristine Pluronic F127 mixed in different ratios as surfactants in the nanoprecipitation experiments.…”

Section: Preparation and Characterization Of Nanoparticlesmentioning

confidence: 99%

Microfluidic-assisted preparation of RGD-decorated nanoparticles: exploring integrin-facilitated uptake in cancer cell lines

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This study is about fine tuning the targeting capacity of peptide-decorated nanoparticles to discriminate between cells that express different integrin make-ups. Using microfluidic-assisted nanoprecipitation, we have prepared poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles with a PEGylated surface decorated with two different arginine-glycine-aspartic acid (RGD) peptides: one is cyclic (RGDFC) and has specific affinity towards α v β 3 integrin heterodimers; the other is linear (RGDSP) and is reported to bind equally α v β 3 and α 5 β 1. We have then evaluated the nanoparticle internalization in two cell lines with a markedly different integrin fingerprint: ovarian carcinoma A2780 (almost no α v β 3 , moderate in α 5 β 1) and glioma U87MG (very high in α v β 3 , moderate/high in α 5 β 1). As expected, particles with cyclic RGD were heavily internalized by U87MG (proportional to the peptide content and abrogated by anti-α v β 3) but not by A2780 (same as PEGylated particles). The linear peptide, on the other hand, did not differentiate between the cell lines, and the uptake increase vs. control particles was never higher than 50%, indicating a possible low and unselective affinity for various integrins. The strong preference of U87MG for cyclic (vs. linear) peptide-decorated nanoparticles was shown in 2D culture and further demonstrated in spheroids. Our results demonstrate that targeting specific integrin make-ups is possible and may open the way to more precise treatment, but more efforts need to be devoted to a better understanding of the relation between RGD structure and their integrinbinding capacity. Integrins are targetable receptors. They are transmembrane glycoproteins, which connect cell bodies to pericellular structures and therefore are critical in cell-cell and cell-environment interactions 1. Structurally, they are heterodimeric proteins composed of non-covalently linked α and β subunits 2. To date 18α and 8β subunits, and 24 different heterodimers have been reported in humans, with each heterodimer displaying unique binding properties, tissue distribution, and biological functions 1 ,3. Although integrins are virtually ubiquitous, their heterodimeric identity and level of expression are a physio-pathological signature, which has a specific relevance in cancer 4 , e.g. in the formation of metastatic niches or in angiogenetic processes 5. Most studies have focused either on integrins in peritumoral environments, e.g. on endothelial cells (ECs), critical to (neo)angiogenesis, or on those directly present on tumor cells 6. It is now well known that α v-containing integrins are highly expressed in both scenarios, but poorly expressed on healthy cells 7. In particular, α v β 3 (e.g. in pro-tumoral ECs) is the most abundant integrin capable of regulating angiogenesis 8. Among other heterodimers, also α 5 β 1 has been

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“…Microfluidics was used to provide reproducible nanoparticle synthesis with precisely controlled parameters (low variation) and was compared to a conventional emulsification method that typically displays large batch to batch variation [ 27 ]. In addition, previous PLGA-based nano-systems prepared using microfluidics have explored only one or two polymer components [ 28 , 29 ]. However, in this study a novel approach using a benchtop NanoAssemblr™ was used to attempt the synthesis using three polymers and a surfactant.…”

Section: Introductionmentioning

confidence: 99%

Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques

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Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.

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Nanomanufacturing through microfluidic-assisted nanoprecipitation: Advanced analytics and structure-activity relationships

Cited by 43 publications

References 40 publications

PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters

PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters

Microfluidic-assisted preparation of RGD-decorated nanoparticles: exploring integrin-facilitated uptake in cancer cell lines

Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques

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