Biocompatible hydrogels have many applications, ranging from contact lenses to tissue engineering scaffolds. In most cases, rigorous sterilization is essential. Herein we show that a biocompatible ...diblock copolymer forms wormlike micelles via polymerization-induced self-assembly in aqueous solution. At a copolymer concentration of 10.0 w/w %, interworm entanglements lead to the formation of a free-standing physical hydrogel at 21 °C. Gel dissolution occurs on cooling to 4 °C due to an unusual worm-to-sphere order–order transition, as confirmed by rheology, electron microscopy, variable temperature 1H NMR spectroscopy, and scattering studies. Moreover, this thermo-reversible behavior allows the facile preparation of sterile gels, since ultrafiltration of the diblock copolymer nanoparticles in their low-viscosity spherical form at 4 °C efficiently removes micrometer-sized bacteria; regelation occurs at 21 °C as the copolymer chains regain their wormlike morphology. Biocompatibility tests indicate good cell viabilities for these worm gels, which suggest potential biomedical applications.
A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from ...a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by 1H NMR spectroscopy and relatively low diblock copolymer polydispersities (M w/M n < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMA x diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG113-PHPMA x phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications.
Small angle X-ray scattering (SAXS), electrospray ionization charge detection mass spectrometry (CD-MS), dynamic light scattering (DLS), and transmission electron microscopy (TEM) are used to ...characterize poly(glycerol monomethacrylate)55-poly(2-hydroxypropyl methacrylate) x (G55-H x ) vesicles prepared by polymerization-induced self-assembly (PISA) using a reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization formulation. A G55 chain transfer agent is utilized to prepare a series of G55-H x diblock copolymers, where the mean degree of polymerization (DP) of the membrane-forming block (x) is varied from 200 to 2000. TEM confirms that vesicles with progressively thicker membranes are produced for x = 200–1000, while SAXS indicates a gradual reduction in mean aggregation number for higher x values, which is consistent with CD-MS studies. Both DLS and SAXS studies indicate minimal change in the overall vesicle diameter between x = 400 and 800. Fitting SAXS patterns to a vesicle model enables calculation of the membrane thickness, degree of hydration of the membrane, and the mean vesicle aggregation number. The membrane thickness increases at higher x values, hence the vesicle lumen must become smaller if the external vesicle dimensions remain constant. Geometric considerations indicate that this growth mechanism lowers the total vesicle interfacial area and hence reduces the free energy of the system. However, it also inevitably leads to gradual ingress of the encapsulated water molecules into the vesicle membrane, as confirmed by SAXS analysis. Ultimately, the highly plasticized membranes become insufficiently hydrophobic to stabilize the vesicle morphology when x exceeds 1000, thus this PISA growth mechanism ultimately leads to vesicle “death”.
RAFT dispersion polymerization is used to prepare diblock copolymer nano-objects using a poly(methacrylic acid) macromolecular chain transfer agent (PMAA macro-CTA) as the steric stabilizer and AIBN ...initiator at 70 °C. The core-forming block is a 1:1 alternating copolymer comprising styrene (St) and N-phenylmaleimide (NMI), and the continuous phase is an ethanol/1,4-dioxane mixture. The 1,4-dioxane cosolvent is essential for this formulation because it aids solubilization of the NMI comonomer within the growing diblock copolymer micelles. Even so, kinetic studies reveal a significant retardation effect once micellar nucleation has occurred. More importantly, the relatively high glass transition temperature of the P(St-alt-NMI) core-forming block (T g = 219 °C) has an interesting influence on the evolution of the copolymer morphology with conversion. At the polymerization temperature of 70 °C, this alternating copolymer is so stiff that 2D lamellae are formed, rather than the vesicular phase that is commonly observed for other RAFT dispersion polymerization formulations. A detailed phase diagram is reported for a series of PMAA79–P(St-alt-NMI) x diblock copolymers, which enables the reproducible synthesis of pure spheres, worms, and the lamellar phase. It is also noteworthy that the worm phase region is unusually broad compared to previous polymerization-induced self-assembly (PISA) formulations. The worms are relatively short and stiff but form free-standing gels above 9% w/w. Increasing the mean degree of polymerization of the core-forming block leads to stronger, more brittle gels. On transferring the diblock copolymer nano-objects into water via dialysis, highly negative zeta potentials are observed above the pK a of the PMAA stabilizer chains, regardless of the copolymer morphology. Thermogravimetric analyses indicate that these diblock copolymer nano-objects have relatively high thermal stabilities, with little or no mass loss being observed on heating in air up to 347 °C.
A poly(glycerol monomethacrylate) (PGMA) macromolecular chain transfer agent has been utilized to polymerize benzyl methacrylate (BzMA) via reversible addition–fragmentation chain transfer ...(RAFT)-mediated aqueous emulsion polymerization. This formulation leads to the efficient formation of spherical diblock copolymer nanoparticles at up to 50% solids. The degree of polymerization (DP) of the core-forming PBzMA block has been systematically varied to control the mean particle diameter from 20 to 193 nm. Conversions of more than 99% were achieved for PGMA51–PBzMA250 within 6 h at 70 °C using macro-CTA/initiator molar ratios ranging from 3.0 to 10.0. DMF GPC analyses confirmed that relatively low polydispersities (M w/M n < 1.30) and high blocking efficiencies could be achieved. These spherical nanoparticles are stable to both freeze–thaw cycles and the presence of added salt (up to 0.25 M MgSO4). Three sets of PGMA51–PBzMA x spherical nanoparticles have been used to prepare stable Pickering emulsions at various copolymer concentrations in four model oils: sunflower oil, n-dodecane, n-hexane, and isopropyl myristate. A reduction in mean droplet diameter was observed via laser diffraction on increasing the nanoparticle concentration. Finally, the cis diol functionality on the PGMA stabilizer chains has been exploited to demonstrate the selective adsorption of PGMA51–PBzMA100 nanoparticles onto a micropatterned phenylboronic acid-functionalized planar surface. Formation of a cyclic boronate ester at pH 10 causes strong selective binding of the nanoparticles via the cis-diol groups in the PGMA stabilizer chains, as judged by AFM studies. Control experiments confirmed that minimal selective nanoparticle binding occurred at pH 4, or if the PGMA51 stabilizer block was replaced with a poly(ethylene glycol) PEG113 stabilizer block.
Diblock copolymer vesicles are prepared via RAFT dispersion polymerization directly in mineral oil. Such vesicles undergo a vesicle‐to‐worm transition on heating to 150 °C, as judged by TEM and SAXS. ...Variable‐temperature 1H NMR spectroscopy indicates that this transition is the result of surface plasticization of the membrane‐forming block by hot solvent, effectively increasing the volume fraction of the stabilizer block and so reducing the packing parameter for the copolymer chains. The rheological behavior of a 10 % w/w copolymer dispersion in mineral oil is strongly temperature‐dependent: the storage modulus increases by five orders of magnitude on heating above the critical gelation temperature of 135 °C, as the non‐interacting vesicles are converted into weakly interacting worms. SAXS studies indicate that, on average, three worms are formed per vesicle. Such vesicle‐to‐worm transitions offer an interesting new mechanism for the high‐temperature thickening of oils.
A vesicle‐to‐worm transition occurs on heating poly(stearyl methacrylate)13‐poly(benzyl methacrylate)96 block copolymer vesicles in mineral oil to provide a new high‐temperature oil‐thickening mechanism.
This Feature Article focuses on the rational design of ‘shape-shifting’ thermoresponsive diblock copolymer nano-objects prepared using 2‑hydroxypropyl methacrylate, 4‑hydroxybutyl acrylate or ...hydroxybutyl methacrylate. A subtle change in the partial degree of hydration of the permanently insoluble thermoresponsive block drives thermal transitions between spheres, worms, vesicles and lamellae. Potential applications for this fascinating new class of amphiphiles are suggested.
Display omitted
In this Feature Article, we review our recent progress in the design of shape-shifting thermoresponsive diblock copolymer nano-objects, which are prepared using various hydroxyl-functional (meth)acrylic monomers (e.g. 2‑hydroxypropyl methacrylate, 4‑hydroxybutyl acrylate or hydroxybutyl methacrylate) to generate the thermoresponsive block. Unlike traditional thermoresponsive polymers such as poly(N-isopropylacrylamide), there is no transition between soluble and insoluble polymer chains in aqueous solution. Instead, thermally driven transitions between a series of copolymer morphologies (e.g. spheres, worms, vesicles or lamellae) occur on adjusting the aqueous solution temperature owing to a subtle change in the partial degree of hydration of the permanently insoluble thermoresponsive block. Such remarkable self-assembly behavior is unprecedented in colloid science: no other amphiphilic diblock copolymer or surfactant system undergoes such behavior at a fixed chemical composition and concentration. Such shape-shifting nano-objects are characterized by transmission electron microscopy, dynamic light scattering, small-angle X-ray scattering, rheology and variable temperature 1H NMR spectroscopy. Potential applications for this fascinating new class of amphiphiles are briefly considered.
A poly(N,N′-dimethylacrylamide) (PDMAC) precursor is chain-extended via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of diacetone acrylamide (PDAAM) to ...produce PDMAC77-PDAAM40 spherical nanoparticles. Post-polymerization core-crosslinking of such nanoparticles was performed at 20 °C, and the resulting covalently stabilized nanoparticles survive exposure to methanol. The linear and core-crosslinked nanoparticles were subjected to high-shear homogenization in turn in the presence of n-dodecane to form macroemulsions. Subsequent processing of these macroemulsions via high-pressure microfluidization produced nanoemulsions. When using the core crosslinked nanoparticles, the droplet diameter was strongly dependent on the copolymer concentration. This indicates that such nanoparticles remain intact under the processing conditions, leading to formation of genuine Pickering nanoemulsions with a z-average diameter of 244 ± 60 nm. In contrast, the linear nanoparticles undergo disassembly to afford molecularly dissolved diblock copolymer chains, which stabilize oil droplets of 170 ± 59 nm diameter. The long-term stability of these two types of n-dodecane-in-water nanoemulsions with respect to Ostwald ripening was examined using analytical centrifugation. When prepared at the same copolymer concentration, Pickering nanoemulsions stabilized by core-crosslinked nanoparticles proved to be significantly more stable than the nanoemulsion stabilized by the amphiphilic PDMAC77-PDAAM40 chains. Moreover, higher copolymer concentrations led to a significantly faster rate of droplet growth. This is attributed to excess copolymer facilitating the diffusion of n-dodecane through the aqueous phase. Finally, analytical centrifugation is used to assess the long-term stability of the analogous squalane-in-water nanoemulsions. These systems are much more stable than the corresponding n-dodecane-in-water nanoemulsions, regardless of whether the copolymer is adsorbed as sterically stabilized nanoparticles or surface-active chains.
PDF
