Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney.

In our previous paper, we demonstrated the ex vivo studies of non-toxic liposome-nanogel systems by which the long-term drug release could be provided from hybrid systems for the 5-fluorouracil (5-FU) drug molecule. The aim of this study was the in vivo magnetic targeting of 5-FU-loaded Fe3O4 nanoparticles including DPPC liposome-based PEGylated nanogels (5-FU loaded Fe3O4LPN) to breast cancer tissue and the investigation of the treatment and cytotoxic effects of that hybrid system to the liver and kidney in CD-1 mice using an external magnetic field. The effectiveness of the control, 5-FU group, Fe3O4LPN, and 5-FU-loaded Fe3O4LPN systems was evaluated using histopathology in terms of p53, ESR, PRG and C-erB-2, and qRT-PCR in terms of TYMS, ESR-1, RPG, and EGRF. Also, the cytotoxicity was analyzed by histopathological evaluation of kidney and liver tissues. Caspase-3 and caspase-9 evaluations were performed by qRT-PCR. The creatinine and ALT levels were also evaluated by comparing the blood samples of all groups. A total of 300-nm TEM-sized Fe3O4LNP hybrid system was successfully prepared. That system significantly decreased the TYMS and ESR1 levels after treatment process and increased the levels of p53 expression. The levels of caspase-3 mRNA did not change during the treatment, but the level of caspase-9 mRNA level was significantly decreased. The magnetically targeted liposome-based nanogel hybrid system is promising an effective therapy for the breast tumor with less liver and kidney damage. This Fe3O4LNP hybrid system could be useful for the similar small molecules.

Biologically Functional Ultrathin Films Made of Zwitterionic Block Copolymer Micelles.

We report the preparation of ultrathin coatings of zwitterionic block copolymer micelles and a comparison of their protein adsorption, adhesiveness, and antibacterial properties. Zwitterionic block copolymer micelles were obtained through pH-induced self-assembly of poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate- b-2-(diisopropylamino)ethyl methacrylate] (ßPDMA- b-PDPA) at pH 7.5. ßPDMA- b-PDPA micelles with zwitterionic ßPDMA-corona and pH-responsive PDPA-core were then used as building blocks to prepare layer-by-layer (LbL) assembled multilayer films together with hyaluronic acid (HA), tannic acid (TA), or poly(sodium 4-styrenesulfonate) (PSS). Protein adsorption tests showed that 3-layer ßPDMA- b-PDPA micelles/HA films were the most effective to reduce the adhesion of BSA, lysozyme, ferritin, and casein. In contrast, ßPDMA- b-PDPA micelles/TA films were the most attractive surfaces for protein adsorption. Bacterial antiadhesive tests against a model Gram-negative bacterium, Escherichia coli, and a model Gram-positive bacterium, Staphylococcus aureus, were in good agreement with the protein adsorption properties of the films. The differences in the antiadhesive properties between these three different film systems are discussed within the context of chemical nature and the functional chemical groups of the polyanions, layer number, and surface morphology of the films. Multilayers were found to lose their antiadhesiveness in the long term. However, by taking advantage of the pH-responsive hydrophobic micellar cores, we show that an antibacterial agent could be loaded into the micelles and multilayers could exhibit antibacterial activity in the long term especially at moderately acidic conditions. In contrast to antiadhesive properties, no significant differences were recorded in the antibacterial properties between the different film types.

Use of Sulfobetaine-Based Block Copolymer as Stabilizer in Silver Nanoparticle Production and Catalytic Activity Studies.

A zwitterionic sulfobetaine-based diblock copolymer was successfully synthesized and used in the preparation and stabilization of Ag nanoparticles (AgNPs). For the related block copolymer, a precursor AB type diblock copolymer was synthesized via atom transfer radical polymerization by using a MPEG-based ATRP macroinitiator and 2-(N-dimethylamino)ethyl methacrylate (DMA) comonomer. Tertiary amine residues of PDMA blocks in poly(ethylene glycol) methyl ether-b-poly[2-(N-diethylamino)ethyl methacrylate] (MPEG-b-PDMA) precursor was then converted to polybetaine structures by reacting with 1,3-propanesultone to obtain poly(ethylene glycol) methyl ether-b-poly[3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate] (MPEG-b-PßDMA) derivative. The resulting block copolymer was successfully used as stabilizer in the chemical and sonochemical synthesis of spherical AgNPs with a diameter in the range of 7.9-9.3 nm. The average diameter of AgNPs synthesized by sonochemical method was smaller than those synthesized by chemical method. The MPEG-b-PßDMA diblock copolymer was determined to be a good stabilizer for AgNPs. The AgNPs dispersion was stable for more than 5 months without any flocculation at room temperature. The catalytic activity of polymer-AgNP dispersion was also investigated in the reduction of p-nitrophenol to p-aminophenol and was found to be quite effective.

Optimization of hyaluronic acid production and its cytotoxicity and degradability characteristics.

In the present study, culture conditions of Streptococcus equi was optimized through Box-Behnken experimental design for hyaluronic acid production. About 0.87 gL-1 of hyaluronic acid was produced under the determined conditions and optimal conditions were found as 38.42 °C, 24 hr and 250 rpm. The validity and practicability of this statistical optimization strategy were confirmed relation between predicted and experimental values. The hyaluronic acid obtained under optimal conditions was characterized. The effects of different conditions such as ultraviolet light, temperature and enzymatic degradation on hyaluronic acid produced under optimal conditions were determined. 118 °C for 32 min of autoclaved HA sample included 63.09 µg mL-1 of d-glucuronic acid, which is about two-fold of enzymatic effect. Cytotoxicity of hyaluronic acid on human dermal cells (HUVEC, HaCaT), L929 and THP-1 cells was studied. In vitro effect on pro or anti-inflammatory cytokine release of THP-1 cells was determined. Although it varies depending on the concentration, cytotoxicity of hyaluronic acid is between 5 and 30%. However, it varies depending on the concentration of hyaluronic acid, TNF-α release was not much increased compared to control study. Consequently, purification procedure is necessary to develop and it is worth developing the bacterial hyaluronic acid.

pH-responsive intermediary layer cross-linked micelles from zwitterionic triblock copolymers and investigation of their drug-release behaviors.

ABC-type triblock copolymers, namely poly[(ethylene glycol)methyl ether]-block-poly(tert-butyl methacrylate)-block-poly[2-N-(diisopropylamino)ethyl methacrylate] (MPEG-b-PBuMA-b-PDPA), were first synthesized and then the middle blocks were successfully converted into poly(methacrylic acid) to obtain MPEG-b-PMAA-b-PDPA zwitterionic triblock copolymers. These block copolymers were soluble in water and formed micellar aggregates with complex cores via hydrogen bonding interactions between MPEG and PMAA blocks below pH 4.0. When the pH was between 5.0 and 7.0, due to charge compensation between partially protonated PDPA and partially ionized PMAA blocks, micelles with polyion complex cores were observed. If the solution pH was above 8.0, deprotonation of tertiary amine groups provided a hydrophobic character to the PDPA block, which resulted in the formation of PDPA-core micelles while MPEG/anionic PMAA hybrid blocks formed hydrated coronas. Intermediary layer cross-linked (ILCL) micelles from PDPA-core micelles were also prepared by cross-linking the inner PMAA shell. The hydrophobic drug dipyridamole (DIP) was used to investigate the release profile of ILCL micelles. DIP can be loaded to the PDPA cores of the micelles in basic aqueous media. An increase in the degree of cross-linking causes slower release for the model drug. It was concluded that the more complex matrix formation in the intermediary layer of the micelles via cross-linking retards the drug release from the core.

Production of NiMn2O4 hollow spheres and CoFe2O4 bowl-like structures by using block copolymer stabilized polystyrene spheres as a hard template.

The aim of this study is to highlight the use of polystyrene (PS) latexes stabilized with block copolymers as a hard template in the production of metal oxide hollow spheres. PS latexes produced by dispersion polymerization by stabilizing with tertiary amine methacrylate-based diblock copolymer were used as a hard template in the preparation of nickel manganese oxide (NiMn2O4) hollow spheres and cobalt iron oxide (CoFe2O4) bowl-like structures. Thanks to the diblock copolymer stabilizer with tertiary amine functional groups on the PS surface, precursor salts of CoFe2O4 and NiMn2O4 were first homogeneously deposited on the surface of PS latexes with a controlled precipitation technique. Then, metal oxide hollow spheres and bowl-like structures were produced by calcination. XRD results showed that CoFe2O4 and NiMn2O4 structures were successfully obtained after calcination. The thermogravimetric analysis results showed that the CoFe2O4 and NiMn2O4 contents of the hybrid PS spheres were in the range of 26.0-28.6 wt%. SEM images showed that the inorganic-polymer spheres fused with each other after calcination to form larger magnetic CoFe2O4 bowl-like structures. SEM images also indicated successful production of highly rough NiMn2O4 hollow spheres with nanosheets on the surface.

In-situ formation of fluorophore cross-linked micellar thick films and usage as drug delivery material for Propranolol HCl.

Polyethylene glycol monomethyl ether-block-poly(glycidyl methacrylate)-block-poly[2-(diethylamino)ethyl methacrylate] triblock copolymer was synthesized to prepare self-assembled micron sized films via a novel approach named as "phase separated micellar self assembly method". Liquid-air interface self assembly method via slow solvent evaporation was used to obtain micellar films. Cross-linking of polymer films was carried out by diffusion of fluorophore cross-linker into polymer solution from subphase. In-situ micellar formation was triggered via driven forces such as molecular interactions and slow evaporation of solvent. Thiazolo[5,4-d]thiazole based cross-linker fluorophores containing alkali subphases were used to prepare highly fluorescent cross-linked micellar films. Micellar morphologies of the films were characterized with SEM while the cross-sections of fluorophore cross-linked films were observed with TEM analysis to examine diffusion of the dye as nano-sized particles into the polymer film. Convenience and usability of the micellar films as drug delivery material were demonstrated with Propranolol HCl release via UV-Vis spectroscopic studies. Optical properties of the films before and after drug release were determined via photoluminescence spectroscopy to be able to sense the completion of the drug release process. Swelling and shrinkage properties of the films were also determined in different pH values. These highly fluorescent polymer films have great potential as drug delivery materials and biomedical sensing applications.

Novel multiresponsive microgels: synthesis and characterization studies.

The dispersion polymerization of 2-(N-morpholino)ethyl methacrylate (MEMA) in the presence of ethylene glycol dimethylacrylate (EGDMA) cross-linker and diblock copolymer stabilizer in n-hexane afforded sterically stabilized multiresponsive PMEMA microgels. By changing the reaction parameters, a wide range of particle sizes (120-720 nm) was obtained. Both dynamic light scattering and electron microscopy studies confirmed monodisperse spherical morphologies. These microgels had a response to the solution pH, temperature, and ionic strength. As expected, PMEMA microgels acquired cationic character at low pH because of the protonation of all morpholino groups. Although PMEMA microgels are in a swollen state in both acidic media and at low temperatures, they are in a deswollen state in basic media at high temperatures and in the presence of electrolytes above pH 6. In addition to these multiresponsive behaviors, PMEMA microgels have the ability to swell in various organic solvents. They also interact very well with magnetic particles and gain responsiveness to the magnetic field. Multiresponsive behaviors of PMEMA microgels were investigated by using DLS, UV-vis spectrophotometry, and zeta potentiometry.

Production of LMWH-conjugated core/shell hydrogels encapsulating paclitaxel for transdermal delivery: In vitro and in vivo assessment.

Topical applications that reduce systemic toxic effects while increasing therapeutic efficacy are a promising alternative strategy. The aim of this study was to provide an enhanced transdermal delivery of low molecular weight heparin (LMWH) through the stratum corneum by using cationic carrier as a novel permeation enhancer. Recent studies have shown that heparin-conjugated biomaterials can be effective in inhibiting tumor growth during cancer treatment due to their high ability to bind growth factors. Paclitaxel (PCL) was co-encapsulated into the same cationic carrier for the purpose of improving of therapeutic efficacy for a combined cancer treatment with LMWH. In vitro and in vivo studies showed that the LMWH and PCL release was significantly affected by polymer molecular weight and block composition. Skin penetration tests have indicated that larger amounts of LMWH were absorbed from LMWH-gel conjugate through SC, than aqueous formula. However, it was found that the plasma transition of LMWH released from gel conjugate was lower compared to the plasma concentration of LMWH released from aqueous solution. It is recommended that PCL-loaded LMWH-conjugated core/shell hydrogels can be used as promising drug release systems for transdermal applications that can improve therapeutic efficacy and reduce side effects in a combined cancer treatment.

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.

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.

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.

Bacterial anti-adhesive and pH-induced antibacterial agent releasing ultra-thin films of zwitterionic copolymer micelles.

UNLABELLED: We report on preparation of substrates with dual function coatings, i.e. bacterial anti-adhesive and antibacterial agent releasing polymer films of zwitterionic block copolymer micelles (BCMs). BCMs were obtained by pH-induced self-assembly of poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate-b-2-(diisopropylamino)ethyl methacrylate] (ßPDMA-b-PDPA), resulting in BCMs with zwitterionic ßPDMA-coronae and pH-responsive PDPA-core. These zwitterionic BCMs were then used as building blocks to construct mono- and multi-layer films. We found that the number of layers in the film was critical for the anti-adhesive property and 3-layer films were the most anti-adhesive against a model Gram-positive bacterium, Staphylococcus aureus. Antibacterial activity could be introduced to the films by loading Triclosan into ßPDMA-b-PDPA micelles. Triclosan containing films were effective against Triclosan-sensitive Staphylococcus aureus specifically at moderately acidic conditions due to pH-induced disintegration of the micellar core blocks and release of Triclosan from the surface. Three-layer films also exhibited anti-adhesive property at physiological pH against a model Gram-negative bacterium, Escherichia coli. At moderately acidic pH, the coatings showed a contact antibacterial effect against an isolate of Escherichia coli with low sensitivity to Triclosan only when micellar cores were loaded with Triclosan. Such dual function films can be promising to combat biofouling at the non-homogeneous and/or defective parts of an anti-adhesive coating. Moreover, considering the moderately acidic conditions around an infection site, these multilayers can be advantageous due to their property of pH-induced antibacterial agent release. STATEMENT OF SIGNIFICANCE: This study presents preparation of substrates with dual function ultra-thin coatings of zwitterionic block copolymer micelles which show bacterial anti-adhesive properties against a Gram-positive and a Gram-negative bacterium. Such coatings are also capable of releasing antibacterial compounds in response to pH changes. Films were prepared by self-assembly of polymers at the surface. Our findings showed that zwitterionic micellar coronae introduced bacterial anti-adhesive property to the films, whereas pH-responsive micellar cores enabled release of an antibacterial agent from the surface at acidic pH. Considering the moderately acidic conditions around an infection site, such multilayers can be promising for the coating of implants/medical devices.

Synthesis of branched poly(methyl methacrylate)s via controlled/living polymerisations exploiting ethylene glycol dimethacrylate as branching agent.

With appropriate choice of reaction composition and conditions, copolymerisation of methyl methacrylate and ethylene glycol dimethacrylate using Cu-based ATRP or GTP methodologies yields soluble branched polymers in facile one-pot reactions.

Bacterial anti-adhesive properties of a monolayer of zwitterionic block copolymer micelles.

We report on bacterial anti-adhesive properties of a monolayer of block copolymer micelles (BCMs) with zwitterionic coronae and pH-responsive cores. BCMs were obtained by pH-induced self-assembly of selectively betainized poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate-b-2-(diisopropylamino)ethyl methacrylate] (ßPDMA-b-PDPA) in aqueous solution above neutral pH. Monolayer films were self-assembled at pH 7.5 when ßPDMA-b-PDPA was in the micellar form. Bacterial anti-adhesive properties of the zwitterionic micellar coatings were examined against S. aureus through: i) a macroscopic test based on viable cell counting; ii) direct microscopic visualization of adherent bacteria by live/dead staining and iii) crystal violet staining to evaluate surface adherent biomass. 95% reduction in cell adhesion was observed by microscopy indicating the anti-adhesive properties of ßPDMA-b-PDPA micellar monolayer. Results obtained from the viable cell count assay and crystal violet staining showed similar trends and were in good agreement with the microscopy results. Such coatings are promising to impart both anti-adhesive and antimicrobial properties to a surface due to bacterial anti-adhesive properties of zwitterionic coronae and the potential of pH-responsive cores to release antimicrobial agents.

Synthesis and characterization of water-insoluble statistical copolymer and its application in the development of electrochemical DNA sensor.

Water-insoluble statistical copolymer was synthesized by copolymerization of methyl methacrylate (MMA) with 2-(dimethylamino)ethyl methacrylate (DMA) via group transfer polymerization (GTP). The DMA residues of the precursor P(MMA-co-DMA) statistical copolymer were then quaternized by reacting with methyl iodide under mild conditions to get well-defined P(MMA-co-QDMA) cationic copolymer. Then, P(MMA-co-QDMA) copolymer was successfully used for surface modification of pencil graphite electrode (PGE) to develop a disposable DNA sensor. This P(MMA-co-QDMA) copolymer modified electrode (q-PGE) was examined for electrochemical monitoring of DNA by using differential pulse voltammetry (DPV) in contrast to unmodified one. The effect of both DNA concentration and sonication time was also examined based on the response of q-PGE. The detection limit was calculated to be 8.06 µg/mL at q-PGE. Electrochemical impedance spectroscopy (EIS) was used for the characterization of the surface modification of q-PGE and consequently, the results were found to be in good agreement with the voltammetric measurements.

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.

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.