Film-forming microgels for pH-triggered capture and release

The pH-responsive behavior for a series of lightly cross-linked, sterically stabilized poly(tertiary amine methacrylate)-based latexes adsorbed onto mica and silica was investigated using in situ tapping mode AFM at room temperature. The adsorbed layer structure was primarily determined by the glass transition temperature, T(g), of the latex: poly[2-(diethylamino)ethyl methacrylate]-based particles coalesced to form relatively featureless uniform thin films, whereas the higher T(g) poly[2-(diisopropylamino)ethyl methacrylate] latexes retained their original particulate character. Adsorption was enhanced by using a cationic poly[2-(dimethylamino)ethyl methacrylate] steric stabilizer, rather than a nonionic poly(ethylene glycol)-based stabilizer, since the former led to stronger electrostatic binding to the oppositely charged substrate. Both types of adsorbed latexes acquired cationic microgel character and swelled appreciably at low pH, even those that had coalesced to form films. Fluorescence spectroscopy was used to study the capture of a model hydrophobic probe, pyrene, by these adsorbed latex layers followed by its subsequent release by lowering the solution pH. The repeated capture and release of pyrene through several pH cycles was also demonstrated. Since these poly(tertiary amine methacrylate) latexes are readily prepared by aqueous emulsion polymerization and adsorption occurs spontaneously from aqueous solution, this may constitute an attractive route for the surface modification of silica, mica and other oxides.     

pH-responsive diblock copolymer micelles at the silica/aqueous solution interface: Adsorption kinetics and equilibrium studies

The adsorption behavior of two examples of a weakly basic diblock copolymer, poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate) (PDMA-PDEA), at the silica/aqueous solution interface has been investigated using a quartz crystal microbalance with dissipation monitoring and an optical reflectometer. Dynamic and static light scattering measurements have also been carried out to assess aqueous solution properties of such pH-responsive copolymers. In alkaline solution, core-shell micelles are formed above the critical micelle concentration (cmc) by both copolymers, whereas the chains are molecularly dissolved (as unimers) at all concentrations in acidic solution. As a result, the adsorption behavior of PDMA-PDEA diblock copolymers on silica is strongly dependent on both the copolymer concentration and the solution pH. Below the cmc at pH 9, the cationic PDMA-PDEA copolymers adsorb as unimers and the conformation of the adsorbed polymer is essentially flat. At concentrations just above the cmc, the initial adsorption of copolymer onto the silica is dominated by the unimers due to their faster diffusion compared to the much larger micelles. Rearrangement of the adsorbed unimers and/or their subsequent displacement by micelles from solution is then observed during an equilibration period, and the final adsorbed mass is greater than that observed below the cmc. At concentrations well above the cmc, the much higher proportion of micelles in solution facilitates more effective competition for the surface at all stages of the adsorption process and no replacement of initially adsorbed unimers by micelles is evident. However, the adsorbed layer undergoes gradual rearrangement after initial adsorption. This relaxation is believed to result from a combination of further copolymer adsorption and swelling of the adsorbed layer.     

Cross-linking of cationic block copolymer micelles by silica deposition

Diblock copolymer micelles comprising cationic poly(2-(dimethylamino)ethyl methacrylate) (PDMA) coronas and hydrophobic poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) cores are used as nanosized templates for the deposition of silica from aqueous solution at pH 7.2 and 20 degrees C. Both noncross-linked and shell cross-linked (SCL) micelles can be coated with silica without loss of colloid stability. Under optimized conditions, the silica deposition is confined to the partially quaternized cationic PDMA chains, leading to hybrid copolymer-silica particles of around 35 nm diameter with well-defined core-shell morphologies. 1H NMR studies confirmed that the PDPA cores of these copolymer-silica particles became protonated at low pH and deprotonated at high pH, which suggests possible encapsulation and controlled release applications. Moreover, in situ silica deposition effectively stabilizes the PDPA-PDMA micelles, which remain intact on lowering the solution pH (whereas the original noncross-linked PDPA-PDMA micelles dissociate in acidic solution). This suggests a convenient route to silica-stabilized SCL micelles under mild conditions.     

pH-responsive behavior of selectively quaternized diblock copolymers adsorbed at the silica/aqueous solution interface

The desorption and subsequent pH-responsive behavior of selectively quaternized poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate) (PDMA-PDEA) films at the silica/aqueous solution interface has been characterized. The copolymer films were prepared at pH 9, where micelle-like surface aggregates are spontaneously formed on silica. The subsequent rinse with a copolymer-free electrolyte solution adjusted to pH 9 causes partial desorption of the weakly or non-quaternized copolymers, but negligible desorption for the highly quaternized copolymers. Further rinsing with a pH 4 electrolyte solution results in additional desorption and extension (swelling) of the remaining adsorbed copolymer film normal to the interface. This pH-responsive behavior is reversible for two pH cycles (9-4-9-4) as monitored by both quartz crystal microbalance with dissipation monitoring (QCM-D) and also zeta potential measurements. The magnitude of the pH-responsive behavior depends on the mean degree of quaternization of the PDMA block. Moreover, a combination of contact angle data, zeta potential measurements and in situ atomic force microscopy (AFM) studies indicates that the pH-responsive behavior is influenced not only by the number of cationic binding sites on the adsorbed copolymer chains but also by the adsorbed layer structure.     

Incorporation of block copolymer micelles into multilayer films for use as nanodelivery systems

This work demonstrates the potential application of stimulus responsive block copolymer micelles as triggerable delivery systems for use within multilayer films. Cationic, pH-responsive micelles of poly[2-(dimethylamino)ethyl methacrylate-block-poly(2-(diethylamino)ethyl methacrylate)] (PDMA-PDEA) were deposited on anionic polystyrene latex particles. The charge reversal of the surface and the amount of adsorbed polymer were monitored by zeta potential measurements and colloidal titrations, respectively. Prior to adsorption, the PDMA-PDEA micelles were loaded with a hydrophobic dye, and UV-vis spectroscopy was used to determine the amount of dye encapsulated within a monolayer of micelles. It was found that subtle chemical modification of the PDMA-PDEA diblock copolymer via permanent quaternization of the PDEA block results in micelles with tunable loading capacities. Multilayers of cationic micelles of partially quaternized PDMA-PDEA and anionic polyelectrolyte (poly(sodium 4-styrene sulfonate)) were deposited on the surface of polystyrene latex particles by sequential adsorption. UV-vis analysis of the dye present within the multilayer after the addition of each layer demonstrates that the micelles are sufficiently robust to retain encapsulated dye after multiple adsorption/washing cycles and can thus create a film that can be increasingly loaded with dye as more micelle layers are adsorbed. Multiple washing cycles were performed on micellar monolayers of PDMA-PDEA to demonstrate how such systems can be used to bring about triggerable release of actives. When performing several consecutive washing steps at pH 9.3, the micelle structure of the PDMA-PDEA micelles in the monolayer is retained, resulting in only a small reduction in the amount of encapsulated dye. In contrast, washing at pH 4, the structure of the micelle layers is severely disrupted, resulting in a fast release of the encapsulated dye into the bulk. Finally, if a sufficient number of micelle/homopolyelectrolyte layers are adsorbed, it is possible to selectively dissolve the latex template, resulting in hollow capsules.     

Characterizing the pH-responsive behavior of thin films of diblock copolymer micelles at the silica/aqueous solution interface

The pH-responsive behavior of cationic diblock poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate) copolymer micelles adsorbed at the silica/aqueous solution interface has been characterized. The micellar morphology of this copolymer, initially adsorbed at pH 9, can be dramatically altered by lowering the solution pH. The original micelle-like morphology of the adsorbed copolymer chains at pH 9 completely disappears as the pH is decreased to 4, and a brush-like layer structure is produced. This change results from protonation of the copolymer chains: the subsequent electrostatic repulsions within the film drive the copolymer chains to expand into the aqueous phase. Returning the solution pH from 4 to 9 causes this brush-like layer to collapse, with atomic force microscopy images suggesting degradation of the film. Hence, the pH-responsive behavior of the copolymer film exhibits irreversible morphological changes. Measurements of the adsorbed/desorbed amounts of the copolymer film were conducted using both a quartz crystal microbalance with dissipation monitoring (QCM-D) and optical reflectometry (OR). After an initial rinse at both pH values, the OR adsorbed mass becomes almost constant during subsequent pH cycling, whereas the corresponding QCM-D adsorbed mass changes significantly but reversibly in response to the solution pH. Since the QCM-D measures a bound mass that moves in tandem with the surface, the discrepancy with the OR data is due to changes in the amount of bound water in the copolymer film as a result of the pH-induced changes in surface morphology. The larger effective mass observed at pH 4 suggests that the brush-like layer contains much more entrapped water than the micellar films at pH 9. The pH dependence of the contact angle of the adsorbed film is consistent with the changes observed using the other techniques, regardless of whether the solution pH is altered in situ or the aqueous solution is completely replaced. In fact, comparison of these two approaches provides direct evidence of the exposure of adsorbed micelle core blocks to the solution during pH cycling and the concomitant impact upon all the other measurements.     

Comparison of the adsorption of cationic diblock copolymer micelles from aqueous solution onto mica and silica

The similarities and differences in the adsorption behavior of diblock poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate) (XqPDMA-PDEA, where X refers to a mean degree of quaternization of the PDMA of either 0, 10, 50, or 100 mol%) copolymers at the mica/ and silica/aqueous solution interfaces have been investigated. These diblock copolymers form core-shell micelles with the PDEA chains located in the cores and the more hydrophilic PDMA chains forming the cationic micelle coronas at pH 9. These micelles adsorb strongly onto both mica and silica due to electrostatic interactions. In situ atomic force microscopy (AFM) has demonstrated that the mean spacing and the dimension of the adsorbed micelles depend on both the substrate and the mean degree of quaternization of the PDMA blocks. In particular, the morphology of the adsorbed nonquaternized 0qPDMA-PDEA copolymer micelles is clearly influenced by the substrate type: these micelles form a disordered layer on silica, while much more close-packed, highly ordered layers are obtained on mica. The key reasons for this difference are suggested to be the ease of lateral rearrangement for the copolymer micelles attached to the solid substrates and the relative rates of relaxation of the coronal PDMA chains.     

Adsorption characteristics of zwitterionic diblock copolymers at the silica/aqueous solution interface

The adsorption of a zwitterionic diblock copolymer, poly(2-(diethylamino)ethyl methacrylate)-block-poly(methacrylic acid) (PDEA59-PMAA50), at the silica/aqueous solution interface has been characterised as a function of pH. In acidic solution, this copolymer forms core-shell micelles with the neutral PMAA chains being located in the hydrophobic cores and the protonated PDEA chains forming the cationic micelle coronas. In alkaline solution, the copolymer forms the analogous inverted micelles with anionic PMAA coronas and hydrophobic PDEA cores. The morphology of the adsorbed layer was observed in situ using soft-contact atomic force microscopy (AFM): this technique suggests the formation of a thin adsorbed layer at pH 4 due to the adsorption of individual copolymer chains (unimers) rather than micelle aggregates. This is supported by the remarkably low dissipation values and the relatively low degrees of hydration for the adsorbed layers, as estimated using a combination of quartz crystal microbalance with dissipation monitoring (QCM-D) and optical reflectometry (OR). In alkaline solution, analysis of the adsorption data suggests a conformation for the adsorbed copolymers where one block projects normal to the solid/liquid interface; this layer consists of a hydrophobic PDEA anchor block adsorbed on the silica surface and an anionic PMAA buoy block extending into the solution phase. Tapping mode AFM studies were also carried out on the silica surfaces after removal from the copolymer solutions and subsequent drying. Interestingly, in these cases micelle-like surface aggregates were observed from both acidic and alkaline solutions. The lateral dimension of the aggregates seen is consistent with the corresponding hydrodynamic diameter of the copolymer micelles in bulk solution. The combination of the in situ and ex situ AFM data provides evidence that, for this copolymer, micelle aggregates are only seen in the ex situ dry state as a result of the substrate withdrawal and drying process. It remains unclear whether these aggregates are caused by micelle deposition at the surface during the substrate withdrawal from the solution or as a result of unimer rearrangements at the drying front as the liquid recedes from the surface.     

Effects of copolymer concentration and chain length on the pH-responsive behavior of diblock copolymer micellar films

The pH-responsive behavior of adsorbed diblock copolymer films of PDMA-PDEA (poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate)) on silica has been characterized using a quartz crystal microbalance with dissipation monitoring (QCM-D), an optical reflectometer (OR) and an atomic force microscope (AFM). The copolymer was adsorbed at pH 9 from various copolymer concentrations; QCM-D measurements indicate that the level of desorption when rinsed at pH 9 depends on the initial copolymer concentration. The adsorbed films produced at pH 9 generally have low charge densities; adjusting the solution pH to 4 results in a significant protonation of the constituent copolymers and a related interfacial structural change for the copolymer film. OR studies show no significant change during pH cycling, while QCM-D measurements indicate that the adsorbed mass and dissipation alter dramatically in response to the solution pH. The difference between the QCM-D adsorbed masses and dissipation values at pH 4 and 9 were found to be dependent on the initial copolymer concentration. This is due to differences in the initial conformations within the adsorbed copolymer layers at pH 9. The effect of the PDMA chain length on the pH-responsive behavior has also been studied; both the QCM-D adsorbed mass and dissipation of PDMA54-PDEA24 (shorter PDMA block) at pH 4 and 9 were observed to be greater than those of PDMA9X-PDEA2Y (longer PDMA block). This suggests that the normal extension of the adsorbed PDMA54-PDEA24 copolymer films is more significant than that of the PDMA9X-PDEA2Y films on silica.     

pH-responsive aqueous foams stabilized by hairy latex particles

Polystyrene (PS) latex particles carrying pH-responsive poly[2-(diethylamino)ethyl methacrylate] (PDEA) hair (PDEA-PS particles) were synthesized by dispersion polymerization and characterized in terms of diameter, diameter distribution, morphology, chemical composition, surface chemistry, and pH-response using scanning electron microscopy (SEM), elemental microanalysis, (1)H nuclear magnetic resonance spectroscopy, the laser diffraction method, and zeta potential measurements. The hairy particles can act as pH-responsive stabilizers of aqueous foams by adsorption at the air-water surface. Above pH 8.0, where particles have nonprotonated PDEA hair, which is relatively hydrophobic, particle-stabilized foams are stable for at least 1 month. Optical microscopy and SEM confirmed that flocculated PDEA-PS latex particles were adsorbed at the air-water interface and stabilized the aqueous foams. At pH 6.1 and 7.1, relatively stable foams can be prepared that remain stable for at least 24 h. SEM studies indicated that the PDEA-PS particles were adsorbed at the air-water interface as a monolayer at pH 6.1. At pH 5.1 and 3.1, where the particles have cationic water-soluble PDEA hairs with hydrophilic character, no foam was formed. Rapid defoamation can be induced by lowering the solution pH; the addition of acid caused the in situ protonation of 2-(diethylamino)ethyl methacrylate residues, which impart water-soluble hydrophilic character to the PDEA hair, and the PDEA-PS particles desorbed from the air-water interface. The foaming and defoaming cycles could be repeated at least five times.     

Synthesis and characterization of shell cross-linked micelles with hydroxy-functional coronas: a pragmatic alternative to dendrimers?

Shell cross-linked (SCL) micelles with hydroxy-functional coronas have been constructed in aqueous solution by exploiting the micellar self-assembly behavior of a new thermoresponsive ABC triblock copolymer. This copolymer was prepared via atom transfer radical polymerization in a convenient one-pot synthesis and comprised a thermoresponsive core-forming poly(propylene oxide) (PPO) block, a cross-linkable central poly(2-(dimethylamino)ethyl methacrylate) (DMA) block, and a hydroxy-functional outer block based on poly(glycerol monomethacrylate) (GMA). DMF GPC analysis confirmed a unimodal molecular weight distribution for the PPO-PDMA-PGMA triblock copolymer precursor, with an M(n) of 12 100 and a polydispersity of approximately 1.26. This copolymer dissolved molecularly in aqueous solution at 5 degrees C but formed micelles with hydroxy-functional coronas above a critical micelle temperature of around 12 degrees C, which corresponded closely to the cloud point of the PPO macroinitiator. Cross-linking of the DMA residues using 1,2-bis(2-iodoethoxy)ethane produced SCL micelles that remained intact at 5 degrees C, i.e., below the cloud point of the core-forming PPO block. Dynamic light scattering studies confirmed that the SCL micelle diameter could be varied depending on the temperature employed for cross-linking: smaller, more compact SCL micelles were formed at higher temperatures, as expected. Since cross-linking involved quaternization of the DMA residues, the SCL micelles acquired cationic surface charge as judged by aqueous electrophoresis studies. These cationic SCL micelles were adsorbed onto near-monodisperse anionic silica sols, which were used as a model colloidal substrate. Thermogravimetric analyses indicated a SCL micelle mass loading of 2.5-4.4%, depending on the silica sol diameter and the initial micelle concentration. Aqueous electrophoresis measurements confirmed that surface charge reversal occurred after adsorption of the SCL micelles, and scanning electron microscopy studies revealed a uniform coating of SCL micelles on the silica particles.     

Characterization of layer-by-layer self-assembled multilayer films of diblock copolymer micelles

The in situ layer-by-layer (LbL) self-assembly of low Tg diblock copolymer micelles onto a flat silica substrate is reported. The copolymers used here were a cationic poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate) (50qPDMA-PDEA; 50q refers to a mean degree of quaternization of 50 mol % for the PDMA block) and zwitterionic poly(methacrylic acid)-block-poly(2-(diethylamino)ethyl methacrylate) (PMAA-PDEA), which has anionic character at pH 9. Alternate deposition of micelles formed by these two copolymers onto a silica substrate at pH 9 was examined. The in situ LbL buildup of the copolymer micelle films was monitored using zeta potential measurements, optical reflectometry, and a quartz crystal microbalance with dissipation monitoring (QCM-D). For a six layer deposition, complete charge reversal was observed after the addition of each layer. The OR data indicated clearly an increase in adsorbed mass with each additional micelle layer and suggest that some interdiffusion of copolymer chains between layers and/or an increase in the film roughness, and hence in the effective surface area of the micellar multilayers, must take place as the film is built up. QCM-D data indicated that the self-assembled micellar multilayers on a flat silica substrate undergo structural changes over a prolonged period. This is attributed to longer-term interdiffusion of the copolymer chains between the outer two layers after the initial adsorption of each layer is complete. The QCM-D data further suggest that the outer adsorbed layers adopt a progressively more extended conformation, particularly for the higher numbered layers. The morphology of each successive layer was characterized using in situ soft-contact atomic force microscopy, and micelle-like surface aggregates are clearly observed within each layer of the complex film, suggesting the persistence of aggregate structures throughout the multilayer structure.     

Symmetric and asymmetric adsorption of pH-responsive gold nanoparticles onto microgel particles and dispersion characterisation

The interaction between carboxylic acid-stabilised gold nanoparticles (AuNP) and pH-responsive microgels is shown. The microgel particles are a copolymer of N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) and N-isopropylacrylamide (NIPAM). The microgel properties are presented by their hydrodynamic diameter and electrophoretic mobility in response to pH. These microgel particles are pH-responsive under neutral conditions decreasing in diameter beyond pH 7. The dispersion characteristics of AuNP adsorbed onto the microgel network are shown with respect to adsorbed amount and the pH-responsive properties of the AuNP. This data is presented between pH 3 and 6 where the microgel properties remain constant. Asymmetric adsorption of AuNP onto poly(DMAPMA-co-NIPAM) microgels is achieved by adsorption of nanoparticles, from the aqueous phase, onto microgel-stabilised oil-in-water emulsions. These asymmetrically modified microgels display very different dispersion behaviour, in response to pH, due to their dipolar nature.     

聚乙二醇-聚谷氨酸-聚丙氨酸三嵌段共聚物的合成及其胶束的pH-响应性药物控制释放

通过大分子引发剂ω-胺基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和酸性水解制备了一种具有pH-响应性的三嵌段共聚物聚乙二醇-聚谷氨酸-聚丙氨酸(mPEG-PLGA-PLAA).通过核磁共振、ζ-电势、动态光散射、电子显微镜等手段表征了此类三嵌段共聚物的自组装过程及所形成胶束的pH-响应性.使用圆二色谱和红外光谱,分析了胶束结构随环境pH值转变过程中聚氨基酸链段二级结构的变化.以阿霉素作为模型药物,研究了三嵌段共聚物的载药能力和在不同pH条件下的药物释放能力.在碱性条件下,PLGA链段去质子化,链段从疏水性变为亲水性,胶束中间层由于水合作用变得松散,药物释放速率增加;在酸性条件下,PLGA链段质子化,不带电荷,与阿霉素药物分子间的静电相互作用消失.同时,PLGA链段α-螺旋含量增加,形成由链内氢键维持的刚性棒状结构,将链段周围包埋的药物分子"挤出",加速了药物的释放.     

Probing the micellization kinetics of pyrene end-labeled diblock copolymer via a combination of stopped-flow light-scattering and fluorescence techniques

A pyrene end-labeled double hydrophilic diblock copolymer, poly(2-(diethylamino)ethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (Py-PDEA-b-PDMA), was synthesized by sequential monomer addition via oxyanionic polymerization using a 1-pyrenemethanol-based initiator. This diblock copolymer exhibits reversible pH-responsive micellization behavior in aqueous solution, forming PDEA-core micelles stabilized by the soluble PDMA block at neutral or alkaline pH. Taking advantage of the pyrene probe covalently attached to the end of the PDEA block, the pH-induced micellization kinetics of Py-PDEA-b-PDMA was monitored by stopped-flow light scattering using a fluorescence detector. Upon a pH jump from 4.0 to 9.0, both the scattered light intensity and excimer/monomer fluorescence intensity ratios (IE/IM) increase abruptly initially, followed by a more gradual increase to reach plateau values. Interestingly, the IE/IM ratio increases abruptly within the first 10 ms: a triple exponential function is needed to fit the corresponding dynamic trace, leading to three characteristic relaxation time constants (tau(1,fluo) < tau(2,fluo) < tau(3,fluo)). On the other hand, dynamic traces for the scattered light intensity can be well-fitted by double exponential functions: the resulting time constants tau(1,scat) and tau(2,scat) can be ascribed to formation of the quasi-equilibrium micelles and relaxation into their final equilibrium state, respectively. Most importantly, tau(1,scat) obtained from stopped-flow light scattering is in general agreement with tau(2,fluo) obtained from stopped-flow fluorescence. The fastest process (tau(1,fluo) approximately 4 ms) detected by stopped-flow fluorescence is ascribed to the burst formation of small transient micelles comprising only a few chains, which are too small to be detected by conventional light scattering. These nascent micelles undergo rapid fusion and grow into quasi-equilibrium micelles and then slowly approach their final equilibrium state. The latter two processes can be detected by both techniques.     

Synthesis and characterisation of new shell cross-linked micelles with amine-functional coronas

Shell cross-linked (SCL) micelles with amine-functional coronas have been constructed in aqueous solution by exploiting the micellar self-assembly of new thermo-responsive ABC triblock copolymers. These copolymers were prepared via atom transfer radical polymerisation (ATRP) in convenient one-pot syntheses and comprised a thermo-responsive core-forming poly(propylene oxide) [PPO] block, a cross-linkable central poly(glycerol monomethacrylate) [GMA] block and an amine-functional outer block based on either poly(2-(dimethylamino)ethyl methacrylate) [DMA] or poly([2-(methacryloyloxy)ethyl]trimethyl ammonium chloride) [QDMA]. DMF GPC analysis indicated an M_n of 17,700 and an M_w/M_n of 1.46 for the PPO-PGMA-PDMA triblock copolymer. The DMA residues of the PPO-PGMA-PDMA triblock copolymer were reacted with methyl iodide to prepare copolymers with differing degrees of quaternisation. Each triblock copolymer dissolved molecularly in aqueous solution at 5 °C and formed micelles with amine-functional coronas above a critical micelle temperature (CMT) of around 12 °C, which corresponded closely to the cloud point of the PPO macro-initiator. Cross-linking of the GMA residues in the inner shell using divinyl sulfone produced SCL micelles that remained intact at 5 °C, i.e. below the cloud point of the core-forming PPO block. Aqueous electrophoresis studies confirmed that these SCL micelles had considerable cationic surface charge, as expected. The cationic SCL micelles were adsorbed onto a near-monodisperse anionic silica sol, which was used as a model colloidal substrate. Thermogravimetric analyses indicated SCL micelle mass loadings of 6.1-15.5 wt.%, depending on the initial micelle concentration. Aqueous electrophoresis studies confirmed that surface charge reversal occurred on adsorption of the SCL micelles and scanning electron microscopy studies revealed the presence of SCL micelles on the silica particles.     

Synthesis of self-assemble pH-responsive cyclodextrin block copolymer for sustained anticancer drug delivery

Well-defined p H-responsive poly(ε-caprolactone)-graft-β-cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)-co-poly(ethylene glycol) methacrylate amphiphilic copolymers(PCL-g-β-CD-g-P(DMAEMA-co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization(ATRP),ring opening polymerization(ROP) and "click" chemistry.Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy(FTIR),proton nuclear magnetic resonance(1H-NMR),and gel permeation chromatography(GPC).Then,the polymers could selfassemble into micelles in aqueous solution,which was demonstrated by dynamic light scattering(DLS) and transmission electron microscopy(TEM).The p H-responsive self-assembly behavior of these copolymers in water was investigated at different p H values of 7.4 and 5.0 for controlled doxorubicin(DOX) release,and these results revealed that the release rate of DOX could be effectively controlled by altering the p H,and the release of drug loading efficiency(DLE) was up to 88%(W/W).CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility,whereas the DOX-loaded micelles remained with high cytotoxicity for He La cells.Moreover,confocal laser scanning microscopy(CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect.The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX.These results successfully indicated that p H-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.     

Polyelectrolyte multilayers of diblock copolymer micelles with temperature-responsive cores

We report on assembly and stimuli-response behavior of layer-by-layer (LbL) films of pH- and temperature-responsive cationic diblock copolymer micelles (BCMs) of poly(2-(dimethylamino)ethyl methacrylate)-block-poly(N-isopropylacrylamide) (PDMA-b-PNIPAM) and a linear polyanion polystyrene sulfonate (PSS). As a function of solution pH at temperatures above lower critical solution temperature (LCST) of PNIPAM, PDMA-b-PNIPAM micelles have been demonstrated earlier to exhibit an abrupt change in micellar aggregation number and hydrodynamic size between larger and smaller BCMs (LBCMs and SBCMs, respectively). Here, LBCMs or SBCMs were included within LbL films through self-assembly with a polyanion, and film pH and temperature responses were studied using ellipsometry and atomic force microscopy (AFM). Both types of micelle preserved their micellar morphology when adsorbed at the surface of oxidized silicon wafers coated with PSS-terminated precursor layer at a constant pH. Response of adsorbed BCMs to temperature and pH variations was strongly dependent on whether or not BCMs were coated with the PSS layer. While monolayers of LBCMs lost their original dry morphology in response to pH or temperature variations, depositing a PSS layer atop LBCMs inhibited such irreversible restructuring. As a result of wrapping around and strong binding of PSS chains with LBCM micelles, BCM/PSS assemblies preserved their original dry state morphology despite the application of pH and temperature triggers. However, the wet-state film response to pH and temperature stimuli was drastically different. Swelling of BCM/PSS multilayers was strongly affected by temperature but was almost independent of pH due to neutralization of BCM PDMA's coronal charge with PSS. Cycling the temperature below and above PNIPAM's LCST caused PNIPAM chains within BCM cores to swell or collapse, resulting in reversible swelling transitions in the entire BCM/PSS assemblies. Temperature-controlled switching between the hydrophobic and hydrophilic state of assembled micellar cores was also used to regulate the release of a micelle-loaded hydrophobic pyrene dye, whose release rate increased at temperatures below PNIPAM's LCST.     

Synthesis and characterization of novel pH-responsive microgels based on tertiary amine methacrylates

Emulsion polymerization of 2-(diethylamino)ethyl methacrylate (DEA) in the presence of a bifunctional cross-linker at pH 8-9 afforded novel pH-responsive microgels of 250-700 nm diameter. Both batch and semicontinuous syntheses were explored using thermal and redox initiators. Various strategies were evaluated for achieving colloidal stability, including charge stabilization, surfactant stabilization, and steric stabilization. The latter proved to be the most convenient and effective, and three types of well-defined reactive macromonomers were examined, namely, monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA), styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (PDMA50-St), and partially quaternized styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (10qPDMA50-St). The resulting microgels were pH-responsive, as expected. Dynamic light scattering and 1H NMR studies confirmed that reversible swelling occurred at low pH due to protonation of the tertiary amine groups on the DEA residues. The critical pH for this latex-to-microgel transition was around pH 6.5-7.0, which corresponds approximately to the known pKa of 7.0-7.3 for linear PDEA homopolymer. The microgel particles were further characterized by electron microscopy and aqueous electrophoresis studies. Their swelling and deswelling kinetics were investigated by turbidimetry. The PDEA-based microgels were compared to poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) microgels prepared with identical macromonomer stabilizers. These PDPA-based microgels had a lower critical swelling pH of around pH 5.0-5.5, which correlates with the lower pKa of PDPA homopolymer. In addition, the kinetics of swelling for the PDPA microgels was somewhat slower than that observed for PDEA microgels; presumably this is related to the greater hydrophobic character of the former particles.     

Specific interactions improve the loading capacity of block copolymer micelles in aqueous media

Block copolymer micelles find application in many fields as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest molecules and core-forming segments can significantly improve the loading capacity of polymeric micelles. High loading capacities (>100% weight/weight of polymer (w/wp)) were systematically observed for the encapsulation of probes containing weak carboxylic acid groups by micellar nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e., particles whose cargo space exhibits antagonist weak base functions), as demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The esterification of IND yielding to a nonionizable IND ethyl ester derivative (IND-Et) caused an abrupt decrease in the micellar loading capacity down to 10-15% w/wp. Similar results were also obtained when IND was combined with nonionizable block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b-poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was confirmed by 1H NMR measurements. However, the incorporation of high numbers of hydrophobic guest molecules inside polymeric micelles can provoke not only an increase in the hydrodynamic size (2RH) of the objects but also a substantial change in the morphology (transition from spheres to cylinders). The application of the Higuchi model showed that the probe release followed a diffusion-controlled mechanism, and diffusion coefficients (D) on the order of 10-18-10-17 cm2/s were determined for IND release from 1.0 mg/mL PEO113-b-PDPA50 + 100% w/wp IND. Probe release from micelles with weak polybase-based cores can also be triggered by changes in the solution pH.