On the mechanism of formation of vesicles from poly(ethylene oxide)-block-poly(caprolactone) copolymers

Adams, Dave J.; Kitchen, Craig; Adams, Sarah; Furzeland, Steve; Atkins, Derek; Schuetz, Peter; Fernyhough, Christine M.; Tzokova, Nadia; Ryan, Anthony J.; Butler, Michael F.

doi:10.1039/b907628j

Cited by 60 publications

(95 citation statements)

References 55 publications

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“…Unlike degradable polymersomes formed from blending "bio-inert" and hydrolysable components, 28, 29 PEO- b -PCL-based vesicles are fully bioresorbable, 30 leaving no potentially toxic byproducts upon their degradation. In contrast to other degradable (polypeptide-, polyester-, or polyanhydride-based) polymersomes, 24, 25, 31–33 PEO(2K)- b -PCL(12K)-based vesicles are formed through spontaneous self-assembly of the pure amphiphilic diblock copolymer, offering manufacturing advantages in terms of cost and safety. Further, these fully bioresorbable polymersomes possess in vivo drug release kinetics appropriate for potential intravascular drug delivery applications.…”

Section: Introductionmentioning

confidence: 99%

“…37–39 As the optimal particle size for prolonged blood stream circulation is ~80–150 nm, and the intracellular uptake of particles having diameters larger than 1 µm is minimal, 37–39 nanometer-sized bioresorbable vesicles are critical for in vivo drug delivery of encapsulated therapeutics. Congruent with these requirements, Butler and coworkers 25 have further examined the formation of nano-sized vesicles from a handful of commercially available PEO- b -PCL block copolymer compositions featuring mostly small PEO chain lengths (300–2000) and low copolymer molecular weights (M w : 2.6–7.8K) by the co-solvent injection method. 25 …”

Section: Introductionmentioning

confidence: 99%

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Aqueous self-assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) copolymers: disparate diblock copolymer compositions give rise to nano- and meso-scale bilayered vesicles

Wei

Ghoroghchian

et al. 2013

Nanoscale

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Nanoparticles formed from diblock copolymers of FDA approved PEO and PCL have generated considerable interest as in vivo drug delivery vehicles. Herein, we report the synthesis of the most extensive family PEO-b-PCL copolymers that vary over the largest range of number-average molecular weights (Mn: 3.6 – 57K), PEO weight fractions (fPEO: 0.08 – 0.33), and PEO chain lengths (0.75–5.8K) reported to date. These polymers were synthesized in order to establish the full range of aqueous phase behaviours of these diblock copolymers and to specifically identify formulations that were able to generate bilayered vesicles (polymersomes). Cryogenic transmission electron microscopy (cryo-TEM) was utilized in order to visualize the morphology of these structures upon aqueous self-assembly of dry polymer films. Nanoscale polymersomes were formed from PEO-b-PCL copolymers over a wide range of PEO weight fractions (fPEO: 0.14 – 0.27) and PEO molecular weights (0.75 – 3.8K) after extrusion of aqueous suspensions. Comparative morphology diagrams, which describe the nature of self-assembled structures as a function of diblock copolymer molecular weight and PEO weight fraction, show that in contrast to micron-scale polymersomes, which form only from a limited range of PEO-b-PCL diblock copolymer compositions, a multiplicity of PEO-b-PCL diblock copolymer compositions are able to give rise to nanoscale vesicles. These data underscore that PEO-b-PCL compositions that spontaneously form micron-sized polymersomes, as well as those that have previously been reported to form polymersomes via a cosolvent fabrication system, provide only limited insights into the distribution of PEO-b-PCL diblocks that give rise to nanoscale vesicles. The broad range of polymersome-forming PEO-b-PCL compositions described herein suggest the ability to construct extensive families of nanoscale vesicles of varied bilayer thickness, providing the ability to tune the timescales of vesicle degradation and encapsulant release based on the intended in vivo application.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aqueous self-assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) copolymers: disparate diblock copolymer compositions give rise to nano- and meso-scale bilayered vesicles

Wei

Ghoroghchian

et al. 2013

Nanoscale

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“…The diblock copolymer micelles are expected to be kinetically trapped in a binary solvent mixture having a water concentration of 25% v/v. 38 The solution was stirred for 10 minutes at room temperature, then transferred to 3,500 MWCO tubing (Snakeskin), and dialyzed against 2 L of deionized water for two days with at least three exchanges of water.…”

Section: Methodsmentioning

confidence: 99%

Dye Encapsulation in Polynorbornene Micelles

et al. 2015

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The encapsulation efficiency of high-Tg polynorbornene micelles was probed with a hydrophobic dye 2,6-diiodo boron-dipyrromethene (BODIPY). Changes in the visible absorption spectra of aggregated versus monomeric dye molecules provided a probe for assessing encapsulation. Polynorbornene micelles are found to be capable of loading up to one BODIPY dye per ten polymers. As the hydrophilic block size increased in the polymeric amphiphiles, more of the dye was incorporated within the micelles. This result is consistent with the dye associating with the polymer backbone in the shell of the micelles. Encapsulation rate varied significantly with temperature, and a slight dependence on micellar morphology was also noted. Additionally, we report a 740 µs triplet lifetime for the encapsulated BODIPY dye. The lifetime is the longest ever recorded for a BODIPY triplet excited state at room temperature, and is attributed to hindered triplet-triplet annihilation in the high viscosity micellar shell.

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“…Therefore, turbidity was used as an established method for monitoring the critical solvent concentration for micelle formation. 16 The solution was monitored for 4 h, and the increasing turbidity correlated with the appearance of larger particles in the TEM micrographs over time ( Figure 6). A distinct series of morphological transitions (sphere, to cylinder, to network, to vesicle, to LCM) was not observed via TEM in this experiment as a result of the solution not being mixed and local inhomogeneities in solvent conditions, causing nonuniform particle formation and growth.…”

Section: Macromoleculesmentioning

confidence: 97%

“…19 The second is primarily due to miscibility and involves the solvent influence over the initial aggregation number (N agg ) of the assembly event, due to the formation of phase separated droplets upon water addition. 16 The third is on the kinetics of formation where more viscous solvents will reduce unimer exchange during assembly. 71 The three solvents chosen for comparison were DMF (ε = 36.7 F/ m), DMSO (ε = 46.7 F/m), and ACN (ε = 37.5 F/m).…”

Section: Macromoleculesmentioning

confidence: 99%

Phase Diagrams of Polynorbornene Amphiphilic Block Copolymers in Solution

et al. 2015

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We report phase diagrams for amphiphilic block copolymers prepared via ring-opening metathesis polymerization (ROMP). A library of 30 block copolymers with variable hydrophilic functionality, block ratios, and degrees of polymerization was prepared, and the resulting assemblies were analyzed by small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). A phase diagram of the self-assemblies was constructed for each of the various copolymer systems screened, representing the first of its kind for polynorbornene block copolymers in dilute solutions. Furthermore, we take advantage of kinetic control in the preparation of an array of particle morphologies accessed from the same polymer structure. ■ INTRODUCTIONIn the design of nanomaterials, morphology is a key consideration in determining fundamental properties. Examples relevant to soft material design include arranging DNA on micelle coronas to increase resistance to nuclease degradation, 1,2 varying circulation patterns and clearance mechanisms of different particle shapes in vivo, 3−8 and shape effects for cellular uptake of nanoparticles in vitro. 9−11 Given the strong correlation between morphology and function, much effort has been expended in the attempt to define particle structure through the design of block copolymer amphiphiles. 12−18 However, it is known that the conditions under which a given micelle is formulated will greatly influence the outcome despite best efforts to dictate results through chemical structure. 15,16,19−25 Over the past few decades, experimental and theoretical studies have explored properties that contribute to selfassembly events of block copolymers (BCPs) in solution. 16,26−30 It has been established that the nanoparticle morphology is a result of a reduction in free energy achieved via three main parameters: (i) stretching of the hydrophobic core block, (ii) interfacial tension between the core and solvent, and (iii) repulsion between corona strands. 12,15,16,20,26,30,31 Each of these components involves contributions from myriad variables in the polymer structure and environment. To complicate the matter further, a delicate balance and interplay between thermodynamically and kinetically driven solution phase particle formation processes has a large influence over the final morphology of the nanostructure. 13,16,18−20,22−25,27−35 For many kinetically trapped systems, unimer exchange may be so unfavorable that the assemblies generated are stable on a time scale of months or years without outside perturbation, and no change in morphology is observed. 36,37 In contrast to BCPs in the bulk, where the influence of kinetics on morphology is less important, constructing phase diagrams for self-assemblies in solution is particularly challenging given that it is impossible to change one component of the polymer or solution without also perturbing the kinetic landscape of assembly. For example, small changes in core block size will not only alter polymer molecular weight or the hydrophilic−hydrophobi...

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On the mechanism of formation of vesicles from poly(ethylene oxide)-block-poly(caprolactone) copolymers

Cited by 60 publications

References 55 publications

Aqueous self-assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) copolymers: disparate diblock copolymer compositions give rise to nano- and meso-scale bilayered vesicles

Aqueous self-assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) copolymers: disparate diblock copolymer compositions give rise to nano- and meso-scale bilayered vesicles

Dye Encapsulation in Polynorbornene Micelles

Phase Diagrams of Polynorbornene Amphiphilic Block Copolymers in Solution

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