Flow-Directed Assembly of Block Copolymer Vesicles in the Lab-on-a-Chip

Wang, Chih‐Wei; Bains, Aman; Sinton, David; Moffitt, Matthew G.

doi:10.1021/la303655s

Cited by 41 publications

(71 citation statements)

References 33 publications

(63 reference statements)

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“…In our group, we have applied gas–liquid two-phase microfluidic reactors to the production of a wide range of PNP systems, 42 − 44 , 71 − 74 including semicrystalline PCL- b -PEO PNPs for drug delivery. 45 − 47 , 75 Within these reactors, counter-rotating vortices within the liquid phase enhance mixing and introduce flow-variable high-shear “hot spots” which provide top-down control of multiscale structure, 42 including the size, 43 morphology, 44 and internal crystallinity 45 of the resulting PNPs.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Self-Assembly, and Drug Delivery Characteristics of Poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) Copolymers with Variable Compositions of Hydrophobic Blocks: Combining Chemistry and Microfluidic Processing for Polymeric Nanomedicines

Lü

Lindenberger

et al. 2017

ACS Omega

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The synthesis, characterization, and self-assembly of a series of biocompatible poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) amphiphilic block copolymers with variable MCL contents in the hydrophobic block are described. Self-assembly gives rise to polymeric nanoparticles (PNPs) with hydrophobic cores that decrease in crystallinity as the MCL content increases, and their morphologies and sizes show nonmonotonic trends with MCL content. PNPs loaded with the anticancer drug paclitaxel (PAX) give rise to in vitro PAX release rates and MCF-7 GI50 (50% growth inhibition concentration) values that decrease as the MCL content increases. We also show for selected copolymers that microfluidic manufacturing at a variable flow rate enables further control of PAX release rates and enhances MCF-7 antiproliferation potency. These results indicate that more effective and specific drug delivery PNPs are possible through tangential efforts combining polymer synthesis and microfluidic manufacturing.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Self-Assembly, and Drug Delivery Characteristics of Poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) Copolymers with Variable Compositions of Hydrophobic Blocks: Combining Chemistry and Microfluidic Processing for Polymeric Nanomedicines

Lü

Lindenberger

et al. 2017

ACS Omega

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“…All SN-38-PNPs are manufactured using a two-phase gas-liquid microfluidic reactor, which has been described previously by our group. 15,16,[18][19][20][21][22][23][24][25][26][27][28] An interesting feature of this reactor are the highshear "hot spots" in the corners of the liquid plugs which provide flow-variable processing of PNPs downstream of water/copolymer mixing and the resulting self-assembly. In previous work, we demonstrated that changes in the manufacturing flow rate within the microfluidic channels allow the maximum shear rate to be varied, 28 enabling shear processing control of sizes, 20,21 morphologies, 15,22 and drug delivery properties 15,16,18,19,26 of various PNP materials.…”

Section: R a F Tmentioning

confidence: 99%

Microfluidic encapsulation of SN-38 in block copolymer nanoparticles: effect of hydrophobic block composition on loading and release properties

et al. 2019

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A gas–liquid microfluidic reactor was used to prepare polymer nanoparticles (PNPs) containing the drug 7-ethyl-10-hydroxy camptothecin (SN-38) from a series of poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) (P(MCL-co-CL)-b-PEO) amphiphilic block copolymers with variable MCL content in the hydrophobic block. All three copolymers formed spheres with ∼20 nm core diameters by TEM, although some rigid rod-like aggregates were also formed by the PMCL-50 and PMCL-75 copolymers. SN-38 encapsulation efficiencies (EE = 2.7%–3.0%) and loading levels (DL = 2.0%–2.9%) were similar for the three copolymers. In vitro release kinetics became significantly slower as the MCL content increased, with release half times increasing monotonically from 3.4 to 6.2 h as the MCL content of the hydrophobic block increased from 50% to 100%. The ability to systematically tune release half times via controlled variation in the hydrophobic block composition, while maintaining constant PNP size and loading levels, represents an intriguing chemical handle for the optimization of SN-38 nanomedicines.

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“…Moffitt's group developed a gas–liquid microfluidic reactor to produce polystyrene‐ block ‐poly(acrylic acid) (PS‐ b ‐PAA) micelles with various morphologies by employing the ultrahigh‐shear field at the corners of the gas−liquid segmented liquid plugs . These on‐chip shear “hot‐spots” provided a flow‐directed top‐down means to control micelle morphology, by inducing the coalescence/fission of micelles that are meant to possess different off‐chip morphologies and thermodynamic stabilities.…”

Section: Microfluidics For Fabrication Of Sddss With Well‐controlled mentioning

confidence: 99%

Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation

Zhang

Zhu

Shen

2018

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Self-assembled drug delivery systems (sDDSs), made from nanocarriers and drugs, are one of the major types of nanomedicines, many of which are in clinical use, under preclinical investigation, or in clinical trials. One of the hurdles of this type of nanomedicine in real applications is the inherent complexity of their fabrication processes, which generally lack precise control over the sDDS structures and the batch-to-batch reproducibility. Furthermore, the classic 2D in vitro cell model, monolayer cell culture, has been used to evaluate sDDSs. However, 2D cell culture cannot adequately replicate in vivo tissue-level structures and their highly complex dynamic 3D environments, nor can it simulate their functions. Thus, evaluations using 2D cell culture often cannot correctly correlate with sDDS behaviors and effects in humans. Microfluidic technology offers novel solutions to overcome these problems and facilitates studying the structure-performance relationships for sDDS developments. In this Review, recent advances in microfluidics for 1) fabrication of sDDSs with well-defined physicochemical properties, such as size, shape, rigidity, and drug-loading efficiency, and 2) fabrication of 3D-cell cultures as "tissue/organ-on-a-chip" platforms for evaluations of sDDS biological performance are in focus.

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Flow-Directed Assembly of Block Copolymer Vesicles in the Lab-on-a-Chip

Cited by 41 publications

References 33 publications

Synthesis, Self-Assembly, and Drug Delivery Characteristics of Poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) Copolymers with Variable Compositions of Hydrophobic Blocks: Combining Chemistry and Microfluidic Processing for Polymeric Nanomedicines

Synthesis, Self-Assembly, and Drug Delivery Characteristics of Poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) Copolymers with Variable Compositions of Hydrophobic Blocks: Combining Chemistry and Microfluidic Processing for Polymeric Nanomedicines

Microfluidic encapsulation of SN-38 in block copolymer nanoparticles: effect of hydrophobic block composition on loading and release properties

Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation

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