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Size evolution of highly amphiphilic macromolecular solution assemblies via a distinct bimodal pathway.

Kelley EG, Murphy RP, Seppala JE, Smart TP, Hann SD, Sullivan MO, Epps TH - Nat Commun (2014)

Bottom Line: Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent.Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule and protein systems.Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, Delaware 19716, USA [2].

ABSTRACT
The solution self-assembly of macromolecular amphiphiles offers an efficient, bottom-up strategy for producing well-defined nanocarriers, with applications ranging from drug delivery to nanoreactors. Typically, the generation of uniform nanocarrier architectures is controlled by processing methods that rely on cosolvent mixtures. These preparation strategies hinge on the assumption that macromolecular solution nanostructures are kinetically stable following transfer from an organic/aqueous cosolvent into aqueous solution. Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent. The unexpected micelle growth evolves through a distinct bimodal distribution separated by multiple fusion events and critically depends on solution agitation. Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule and protein systems. Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure.

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Cryo-TEM studies of micelle size evolution(a)Cryogenic transmission electron microscopy (cryo-TEM) images showing changes in micelle core radii (Rc) over 21d post-dialysis. The polymer concentration was initially 10mgmL-1, and the THF content was 43% by volume before dialysis. Scale bars represent 100nm. (b) Corresponding histograms of micelle sizes obtained from analysis of cryo-TEM images. The relative percentages of the smaller (Rc<8nm) and larger (Rc≥8nm) core radii populations are shown on the histograms. Sample sizes for each histogram ranged between 450 and 3000 micelles.
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Figure 5: Cryo-TEM studies of micelle size evolution(a)Cryogenic transmission electron microscopy (cryo-TEM) images showing changes in micelle core radii (Rc) over 21d post-dialysis. The polymer concentration was initially 10mgmL-1, and the THF content was 43% by volume before dialysis. Scale bars represent 100nm. (b) Corresponding histograms of micelle sizes obtained from analysis of cryo-TEM images. The relative percentages of the smaller (Rc<8nm) and larger (Rc≥8nm) core radii populations are shown on the histograms. Sample sizes for each histogram ranged between 450 and 3000 micelles.

Mentions: As chain exchange was not prevalent in this PB-PEO system, fusion processes were examined as the other mechanism that could promote micelle reorganization. To visualize the micelle growth, cryo-TEM was employed to follow the temporal evolution of a micelle solution (10 mg mL-1 in 43 % by volume THF) over a 21 d period following cosolvent removal. The resulting micrographs are shown in Fig. 5a, in which the darker domains correspond to the dense PB cores while the fainter halos correspond to the PEO coronas40,41. Note that the hexagonal packing in the Day 10, 16 and 21 samples was an artefact of sample preparation (Supplementary Fig. 2). The core sizes were extracted from the images and the corresponding frequency histograms are shown in Fig. 5b. The core radii at Day 0 were described by a single and nearly monodisperse distribution centred at 5 nm to 6 nm. Surprisingly, a second distinct distribution of core radii centred at 10 nm to 11 nm appeared after 1 d. This second distribution corresponded to an approximate eight-fold increase in core volume or aggregation number from the initial distribution, in which the small and large micelle populations contained aggregation numbers of approximately 100 and 800, respectively (Supplementary Fig. 3). The distinct bimodal distribution persisted throughout 10 d, with the population weighting shifting from the smaller to larger distribution over time. By Day 16 to Day 21, the core size distribution exhibited a single and nearly monodisperse population at 10 nm to 11 nm, consistent with the time scales determined from DLS (Fig. 2). Similar behaviour was found for the samples prepared from 30 % by volume and 50 % by volume THF solutions (Supplementary Fig. 4 and Supplementary Discussion), suggesting that all specimens prepared at high THF contents grew through a fusion-controlled process.


Size evolution of highly amphiphilic macromolecular solution assemblies via a distinct bimodal pathway.

Kelley EG, Murphy RP, Seppala JE, Smart TP, Hann SD, Sullivan MO, Epps TH - Nat Commun (2014)

Cryo-TEM studies of micelle size evolution(a)Cryogenic transmission electron microscopy (cryo-TEM) images showing changes in micelle core radii (Rc) over 21d post-dialysis. The polymer concentration was initially 10mgmL-1, and the THF content was 43% by volume before dialysis. Scale bars represent 100nm. (b) Corresponding histograms of micelle sizes obtained from analysis of cryo-TEM images. The relative percentages of the smaller (Rc<8nm) and larger (Rc≥8nm) core radii populations are shown on the histograms. Sample sizes for each histogram ranged between 450 and 3000 micelles.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4225159&req=5

Figure 5: Cryo-TEM studies of micelle size evolution(a)Cryogenic transmission electron microscopy (cryo-TEM) images showing changes in micelle core radii (Rc) over 21d post-dialysis. The polymer concentration was initially 10mgmL-1, and the THF content was 43% by volume before dialysis. Scale bars represent 100nm. (b) Corresponding histograms of micelle sizes obtained from analysis of cryo-TEM images. The relative percentages of the smaller (Rc<8nm) and larger (Rc≥8nm) core radii populations are shown on the histograms. Sample sizes for each histogram ranged between 450 and 3000 micelles.
Mentions: As chain exchange was not prevalent in this PB-PEO system, fusion processes were examined as the other mechanism that could promote micelle reorganization. To visualize the micelle growth, cryo-TEM was employed to follow the temporal evolution of a micelle solution (10 mg mL-1 in 43 % by volume THF) over a 21 d period following cosolvent removal. The resulting micrographs are shown in Fig. 5a, in which the darker domains correspond to the dense PB cores while the fainter halos correspond to the PEO coronas40,41. Note that the hexagonal packing in the Day 10, 16 and 21 samples was an artefact of sample preparation (Supplementary Fig. 2). The core sizes were extracted from the images and the corresponding frequency histograms are shown in Fig. 5b. The core radii at Day 0 were described by a single and nearly monodisperse distribution centred at 5 nm to 6 nm. Surprisingly, a second distinct distribution of core radii centred at 10 nm to 11 nm appeared after 1 d. This second distribution corresponded to an approximate eight-fold increase in core volume or aggregation number from the initial distribution, in which the small and large micelle populations contained aggregation numbers of approximately 100 and 800, respectively (Supplementary Fig. 3). The distinct bimodal distribution persisted throughout 10 d, with the population weighting shifting from the smaller to larger distribution over time. By Day 16 to Day 21, the core size distribution exhibited a single and nearly monodisperse population at 10 nm to 11 nm, consistent with the time scales determined from DLS (Fig. 2). Similar behaviour was found for the samples prepared from 30 % by volume and 50 % by volume THF solutions (Supplementary Fig. 4 and Supplementary Discussion), suggesting that all specimens prepared at high THF contents grew through a fusion-controlled process.

Bottom Line: Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent.Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule and protein systems.Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, Delaware 19716, USA [2].

ABSTRACT
The solution self-assembly of macromolecular amphiphiles offers an efficient, bottom-up strategy for producing well-defined nanocarriers, with applications ranging from drug delivery to nanoreactors. Typically, the generation of uniform nanocarrier architectures is controlled by processing methods that rely on cosolvent mixtures. These preparation strategies hinge on the assumption that macromolecular solution nanostructures are kinetically stable following transfer from an organic/aqueous cosolvent into aqueous solution. Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent. The unexpected micelle growth evolves through a distinct bimodal distribution separated by multiple fusion events and critically depends on solution agitation. Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule and protein systems. Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure.

Show MeSH
Related in: MedlinePlus