Size controlled polymersomes by continuous self-assembly in micromixers

Thiermann, Raphael; Mueller, Waltraut; Montesinos‐Castellanos, Alejandro; Metzke, D.; Löb, Patrick; Hessel, Volker; Maskos, Michael

doi:10.1016/j.polymer.2012.03.058

Cited by 47 publications

(58 citation statements)

References 36 publications

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“…For example, diameters of spherical poly(butadiene)- block -poly(ethylene oxide) polymersomes can be adjusted between 45 nm and 100 nm by varying the polymer concentration and the mixing rate. [18,19] During the mixing of the water and polymer solution, polymer molecules in the organic phase diffuse into the water phase. As such, increasing the mixing rate (total flow rate of 10 mL/min) drives the polymers to diffuse into the water phase quickly and self-assemble into small polymersomes (50 nm in diameter).…”

Section: Controlling Polymersome Sizementioning

confidence: 99%

Engineering Polymersomes for Diagnostics and Therapy

Leong

Teo

Aakalu

et al. 2018

Adv Healthcare Materials

114

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Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self-assembly of amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer membrane and hydrophilic core, each of which is loaded with a wide array of small and large molecules of interests. As such, polymersomes are increasingly being studied as carriers of imaging probes and therapeutic drugs. Effective delivery of polymersomes necessitates careful design of polymersomes. Therefore, this review article discusses the design strategies of polymersomes developed for enhanced transport and efficacy of imaging probes and therapeutic drugs. In particular, the article focuses on overviewing technologies to regulate the size, structure, shape, surface activity, and stimuli- responsiveness of polymersomes and discussing the extent to which these properties and structure of polymersomes influence the efficacy of cargo molecules. Taken together with future considerations, this article will serve to improve the controllability of polymersome functions and accelerate the use of polymersomes in biomedical applications.

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Section: Controlling Polymersome Sizementioning

confidence: 99%

Engineering Polymersomes for Diagnostics and Therapy

Leong

Teo

Aakalu

et al. 2018

Adv Healthcare Materials

114

View full text Add to dashboard Cite

show abstract

“…the initial polymer concentration, the nature, the water content of the common solvent, the mixing ratios, and the total flow rates. 102,103 Compared to the batch cosolvent method, where mixing efficiency is dependent on the batch volume as well as stirring velocity, micromixer technology enables a very efficient mixing. Thus, even self-assembly of polymers with a small hydrophilic fraction can be performed.…”

Section: Self-assembly Of Polymersomes In Micromixersmentioning

confidence: 99%

“…Accordingly, the resulting vesicles exhibit a larger diameter than those starting at lower polymer concentration. 52,103 Beside the factors as polymer composition, temperature and common solvent, that are dependent on the nature of the polymer and are also valid for the batch process, polymersome size can also be influenced by the mixing parameters as for example the flow rate.…”

Section: Macromoleculesmentioning

confidence: 99%

Techniques To Control Polymersome Size

2015

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Polymersomes as synthetic analogues of liposomes appear frequently in relevant literature as promising candidates for a wide range of different applications including drug delivery, theranostic multitools, and nanoreactors. In particular, as nanotransporters for nanomedical applications in vivo, requirements concerning the reproducible manufacturing and reliable size control are extremely high. This Perspective highlights the importance of size control especially in the context of nanomedicine and gives an overview of the theoretical background of amphiphilic self-assembly leading to different preparation methods, where their feasibility of controlling polymersomes' size is discussed.

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“…The size and shape of these nanocarriers impacts their biodistribution, systemic clearance, cellular internalization, optical properties and overall therapeutic potential [1–3, 27, 28]. Aggregate morphology can be specified by synthesizing block copolymers with a particular hydrophilic weight fraction (typically >45% for polymersomes), kinetically trapping metastable intermediate structures during self-assembly or modulating the vesicles after formation often using shear forces or osmotic pressure gradients [18, 19, 22, 29–31]. These methods have resulted in a wide range of nanostructures with unique properties and applications, including tubule polymersomes, multilamellar nested vesicles and bicontinuous nanostructures [32–35].…”

Section: Introductionmentioning

confidence: 99%

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Allen

Osorio

Liu

et al. 2017

Journal of Controlled Release

141

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Flash nanoprecipitation (FNP) has proven to be a powerful tool for the rapid and scalable assembly of solid-core nanoparticles from block copolymers. The process can be performed using a simple confined impingement jets mixer and provides an efficient and reproducible method of loading micelles with hydrophobic drugs. To date, FNP has not been applied for the fabrication of complex or vesicular nanoarchitectures capable of encapsulating hydrophilic molecules or bioactive protein therapeutics. Here, we present FNP as a single customizable method for the assembly of bicontinuous nanospheres, filomicelles and vesicular, multilamellar and tubular polymersomes from poly(ethylene glycol)-bl-poly(propylene sulfide) block copolymers. Multiple impingements of polymersomes assembled via FNP were shown to decrease vesicle diameter and polydispersity, allowing gram-scale fabrication of monodisperse polymersomes within minutes. Furthermore, we demonstrate that FNP supports the simultaneous loading of both hydrophobic and hydrophilic molecules respectively into the polymersome membrane and aqueous lumen, and encapsulated enzymes were found to be released and remain active following vesicle lysis. As an example application, theranostic polymersomes were generated via FNP that were dual loaded with the immunosuppressant rapamycin and a fluorescent dye to link targeted immune cells with the elicited immunomodulation of T cells. By expanding the capabilities of FNP, we present a rapid, scalable and reproducible method of nanofabrication for a wide range of nanoarchitectures that are typically challenging to assemble and load with therapeutics for controlled delivery and theranostic strategies.

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Size controlled polymersomes by continuous self-assembly in micromixers

Cited by 47 publications

References 36 publications

Engineering Polymersomes for Diagnostics and Therapy

Engineering Polymersomes for Diagnostics and Therapy

Techniques To Control Polymersome Size

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

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