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.     

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.     

Fabrication of multifunctional shell cross-linked micelles for targeting drug release

Thermosensitive amphiphilic poly(N-acroyloxysuccinimide)-b-poly(N-isopropylacrylamide)-b-poly(??-caprolactone) triblock copolymer was synthesized via the combination of reversible addition fragmentation chain transfer and ring-opening polymerization techniques. Shell cross-linked micelle (SCL) was further developed by the addition of cystamine as a di-functional cross-linker into the micellar solution. The persistence of regularly spherical shape against media change demonstrated locked micellar structure resulting from sufficient shell cross-linking. The lower critical solution temperature of the resulting SCL micelles was around 38?°C. The in vitro drug release study was carried out to illustrate the temperature-responsive drug release behaviors. To enhance the internalization to tumor cells, transferring (Tf) was further conjugated to the SCL micelles, and endocytosis experiments further confirmed the efficient uptake of Tf-SCL micelles by tumor cells, indicating that the Tf-SCL micelles would be a promising candidate for tumor-targeted drug delivery.     

Facile strategy for synthesis of silica/polymer hybrid hollow nanoparticles with channels

The silica/polymer hybrid hollow nanoparticles with channels and gatekeepers were successfully fabricated with a facile strategy by using thermoresponsive complex micelles of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP) as the template. In aqueous solution, the complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) formed with the PNIPAM block as the core and the PEG/P4VP blocks as the mixed shell at 45 °C and pH 4.0. After shell cross-linking by 1,2-bis(2-iodoethoxyl)ethane (BIEE), tetraethylorthosilicate (TEOS) selectively well-deposited on the P4VP block and processed the sol-gel reaction. When the temperature was decreased to 4 °C, the PNIPAM block became swollen and further soluble, and the PEG-b-PNIPAM block copolymer escaped from the hybrid nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica at pH 4.0. Therefore, the hybrid hollow silica nanoparticles with inner thermoresponsive PNIPAM as gatekeepers and channels in the silica shell were successfully obtained, which could be used for switchable controlled drug release. In the system, the complex micelles, as a template, could avoid the formation of larger aggregates during the preparation of the hybrid hollow silica nanoparticles. The thermoresponsive core (PNIPAM) could conveniently control the hollow space through the stimuli-responsive phase transition instead of calcination or chemical etching. In the meantime, the channel in the hybrid silica shell could be achieved because of the escape of PEG chains from the hybrid nanoparticles.     

Rapid and precise release from nano-tracted poly(N-isopropylacrylamide) hydrogels containing linear poly(acrylic acid)

We investigated the rapid and precise molecular release from hydrogels in response to dual stimuli. To achieve precise on/off drug release using thermoresponsive poly(N-isopropylacrylamide) hydrogels, we prepared nano-structured semi-IPNs, which consisted of thermosensitive PNIPAAm networks penetrated by pH-responsive poly(acrylic acid) (PAAc) linear chains and perforated to create nano-tracts as a molecular pathway. The present nano-tracted semi-IPNs show a rapid deswelling response to both temperature and pH. Model drug releases were investigated when simultaneous changes in temperature and pH were applied. We observed that the cationic drug was rapidly released and then abruptly discontinued from the nano-tracted semi-IPNs in response to the dual stimuli, and clear release and stopping cycles were repeatedly observed on successive steps. Moreover, the release rates and amount of drug released were controllable by the deswelling speed of the gels and the PAAc content inside the gels. This novel release system using the nano-tracted semi-IPNs may be useful for the high performance, pulsed release of molecules.     

Synthesis and self-assembly behavior of thermoresponsive poly(oligo(ethylene glycol) methyl ether methacrylate)-POSS with tunable lower critical solution temperature

This article reports on the synthesis of a novel amphiphilic polyhedral oligomeric silsesquioxane (POSS) end-capped poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-oligo(ethylene glycol) methacrylate) (POSS-P(MEO₂MA-co-OEGMA)). These thermoresponsive organic–inorganic hybrid polymers exhibit critical phase transition temperature in water, which can be finely tuned by changing the feed ratio of OEGMA and MEO₂MA. The lower critical solution temperature (LCST) of POSS-P(MEO₂MA-co-OEGMA) increases from 31 to 59 °C with the increasing of OEGMA content. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies show that these polymers can self-assemble into spherical micelles with the thermosensitive block into the corona and the POSS forming the core, and larger aggregates are formed when the temperature values are above their LCSTs. These thermoresponsive polymers POSS-P(MEO₂MA-co-OEGMA) with self-assembly behavior and tunable tempetature-responsive property have the potential applications in material science and biotechnology.     

Well‐defined thermoresponsive dendritic polyamide/poly(N‐vinylcaprolactam) block copolymers

The first‐ and second‐generation well‐defined thermoresponsive amphiphilic linear–dendritic diblock copolymers based on hydrophilic linear poly(N‐vinylcaprolactam) and hydrophobic dendritic aromatic polyamide have been synthesized via reversible addition fragmentation chain transfer polymerization of N‐vinylcaprolactam by employing dendritic chain‐transfer agents possessing a single dithiocarbamate moiety at the focal point. These linear–dendritic copolymers exhibit reversible temperature‐dependent phase transition behaviors in aqueous solution as characterized by turbidity measurements using UV–vis spectroscopy. Their lower critical solution temperatures depend on the generation of the dendritic aromatic polyamides and the concentrations of the copolymer solutions. These amphiphilic copolymers are able to form nanospherical micelles in the aqueous solution as revealed by fluorescent spectroscopy, dynamic light scattering, and transmission electron microscope (TEM). The core–shell structure of micelles has been proved by ¹H NMR analyses of the micelles in D2O. The micelles loaded with indomethacin as a model drug showed high‐drug loading capacity and thermoresponsive drug release behavior. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3240–3250     

Flocculation‐resistant multimolecular micelles with thermoresponsive corona from dendritic heteroarm star copolymers

In this article, we report the self‐assembly of flocculation‐resistant multimolecular micelles with thermoresponsive corona from novel dendritic heteroarm star copolymers. The micelles have a core‐shell‐corona structure at room temperature according to pyrene probe fluorescence spectrometry, proton nuclear magnetic resonance (¹H NMR), transmission electron microscopy, and dynamic light scattering measurements. Increasing the temperature above the lower critical solution temperature (LCST), the micelles show high flocculation‐resistant ability resulting from a structure transition from core‐shell‐corona to core‐shell confirmed by a quantitative variable temperature ¹H NMR analysis method using potassium hydrogen phthalate as an external standard. A big volume change of the micelles is observed during the LCST transition. The drug loading and temperature‐dependent release properties of the micelles are also investigated by using coumarin 102 as a model drug, which displays a rapid drug release at a temperature above the LCST. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and characterization of core–shell‐type polymeric micelles from diblock copolymers via reversible addition–fragmentation chain transfer

A method was developed to enable the formation of nanoparticles by reversible addition–fragmentation chain transfer polymerization. The thermoresponsive behavior of polymeric micelles was modified by means of micellar inner cores and an outer shell. Polymeric micelles comprising AB block copolymers of poly(N‐isopropylacrylamide) (PIPAAm) and poly(2‐hydroxyethylacrylate) (PHEA) or polystyrene (PSt) were prepared. PIPAAm‐b‐PHEA and PIPAAm‐b‐PSt block copolymers formed a core–shell micellar structure after the dialysis of the block copolymer solutions in organic solvents against water at 20 °C. Upon heating above the lower critical solution temperature (LCST), PIPAAm‐b‐PHEA micelles exhibited an abrupt increase in polarity and an abrupt decrease in rigidity sensed by pyrene. In contrast, PIPAAm‐b‐PSt micelles maintained constant values with lower polarity and higher rigidity than those of PIPAAm‐b‐PHEA micelles over the temperature range of 20–40 °C. Structural deformations produced by the change in the outer polymer shell with temperature cycles through the LCST were proposed for the PHEA core, which possessed a lower glass‐transition temperature (ca. 20 °C) than the LCST of the PIPAAm outer shell (ca. 32.5 °C), whereas the PSt core with a much higher glass‐transition temperature (ca. 100 °C) retained its structure. The nature of the hydrophobic segments composing the micelle inner core offered an important control point for thermoresponsive drug release and the drug activity of the thermoresponsive polymeric micelles. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3312–3320, 2006     

Nanostructured latex films from poly(butyl methacrylate) latex cross-linked with poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) triblock macro-cross-linker

Biphasic polymer latexes were synthesized by a seeded swelling and polymerization method. The latexes were composed of a poly(butyl methacrylate) core and a poly(ethylene oxide) rich shell cross-linked with poly(ethylene oxide)-poly (propylene oxide)-poly(ethylene oxide) triblock diol diacrylate macro-cross-linker. Nanostructured films were obtained by annealing the biphasic polymer latexes at a temperature between the glass-transition temperatures of the core latex and the cross-linked poly(ethylene oxide) based shell. Atomic force microscope images of the latex film revealed that the poly(butyl methacrylate) core phase is confined in the poly(ethylene oxide)-rich continuous phase with the form of separate nanosized spheres.     

Self‐assembly of thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) micelles for drug delivery

Self‐assembled thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) (PAA‐b‐PNIPAM) micelles for entrapment and release of doxorubicin (DOX) was described. Block copolymer PAA‐b‐PNIPAM associated into core‐shell micelles in aqueous solution with collapsed PNIPAM block or protonated PAA block as the core on changing temperature or pH. Complexation of DOX with PAA‐b‐PNIPAM triggered by the electrostatic interaction and release of DOX from the complexes due to the changing of pH or temperature were studied. Complex micelles incorporated with DOX exhibited pH‐responsive and thermoresponsive drug release profile. The release of DOX from micelles was suppressed at pH 7.2 and accelerated at pH 4.0 due to the protonation of carboxyl groups. Furthermore, the cumulative release of DOX from complex micelles was enhanced around LCST ascribed to the structure deformation of the micelles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5028–5035, 2008     

Synthesis and characterization of well‐defined,amphiphilic poly(N‐isopropylacrylamide)‐ b‐[2‐hydroxyethyl methacrylate‐poly(ϵ‐caprolactone)]n graft copolymers by RAFT polymerization and macromonomer method

The well‐defined, thermosensitive and biodegradable graft copolymers, poly(N‐isopropylacrylamide)‐b‐[2‐hydroxyethyl methacrylate‐poly(ε‐caprolactone)]_n (PNIPAAm‐b‐(HEMA‐PCL)_n) (n = 3 or 9), were synthesized by combining reversible addition‐fragmentation chain transfer polymerization and macromonomer method. The copolymers were able to self‐assemble into micelles in water with low critical micellar concentration and demonstrated temperature sensitivity with a lower critical solution temperature at around 36 °C. Transmission electron microscopy shows that the micelles exhibit a nanosized spherical morphology within a size range of 30–100 nm. The PNIPAAm‐b‐(HEMA‐PCL)₃ copolymer exhibited biodegradation and low cytotoxicity. The paclitaxel‐loaded PNIPAAm‐b‐(HEMA‐PCL)₃ micelles displayed thermosensitive controlled release behavior, which indicates potential as drug carriers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5354–5364, 2007     

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.     

Hierarchically organized micellization of thermoresponsive rod‐coil copolymers based on poly[oligo(ethylene glycol) methacrylate] and poly(ε‐caprolactone)

A series of amphiphilic triblock copolymers, poly[oligo(ethylene glycol) methacrylate]_x‐block‐poly(ε‐caprolactone)‐block‐poly[oligo(ethylene glycol) methacrylate]_x, POEGMA_Co(x), were synthesized. Formation of hydrophobic domains as cores of the micelles was studied by fluorescence spectroscopy. The critical micelle concentrations in aqueous solution were found to be in the range of circa 10^?6 M. A novel methodology by modulated temperature differential scanning calorimetry was developed to determine critical micelle temperature. A significant concentration dependence of cmt was found. Dynamic light scattering measurements showed a bidispersed size distribution. The micelles showed reversible dispersion/aggregation in response to temperature cycles with lower critical solution temperature between 75 and 85 °C. The interplay of the two hydrophobic and one thermoresponsive macromolecular chains offers the chance to more complex morphologies. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis,thermo-responsive micellization and caffeine drug release of novel PBMA-<Emphasis Type="Italic">b</Emphasis>-PNIPAAm block polymer brushes

Brush-like block copolymers with poly(t-butyl methacrylate) (PBMA) and poly(N-isopropylacrylamide) (PNIPAAm) as side arms, PBMA-b-PNIPAAm, were designed and synthesized via a simple free radical polymerization route. The chemical structure and molecular weight of these polymer brushes were characterized and determined by nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectrometry (FTIR) and gel permeation chromatography (GPC). The micellar formation by these polymer brushes in aqueous solutions were detected by a surface tension technique, and the critical micelle concentration (CMC) ranged from 1.53 to 8.06 mg L⁻¹. The morphology and geometry of polymer micelles were investigated by transmission electron microscope (TEM) and dynamic light scattering (DLS). The polymer micelles assume the regularly-spherical core-shell structure with well-dispersed individual nanoparticles, and the particle size was in the range from 36 to 93 nm. The PNIPAAm segments exhibited a thermoreversible phase transition, so the resulting block polymer brushes were temperature-sensitive and the low critical solution temperature (LCST) was determined by UV-vis spectrometer at about 28.82–29.40°C. The characteristic parameters of the polymer micelles such as CMC, micellar size and LCST values were affected by their compositional ratios and the length of hydrophilic or hydrophobic chains. The evaluation for caffeine drug release behavior of the block polymer micelles demonstrated that the self-assembled micelles exhibited thermal-triggered properties in controlled drug release.     

Thermosensitive pluronic micelles stabilized by shell cross-linking with gold nanoparticles

Gold nanoparticles were employed to prepare shell cross-linked Pluronic micelles that exhibit a reversibly thermosensitive swelling/shrinking behavior. Two terminal hydroxyl groups of Pluronic F127 were thiol-functionalized to form self-assembling Pluronic micelles in aqueous solution with exposed -SH groups in an outer shell layer. The thiol groups present in the outer shell were cross-linked by gold nanoparticles synthesized through NaBH4 reduction of gold precursor anions. The resultant shell cross-linked gold-Pluronic micelles exhibited a temperature-dependent volume transition: their hydrodynamic diameter was changed from 157.1 +/- 15.6 nm at 15 degrees C to 53.4 +/- 5.5 nm at 37 degrees C as determined by dynamic light scattering. The critical micelle temperature measured by a pyrene solubilization technique suggested that the reversible swelling/shrinking behavior of the micelles was caused by hydrophobic interactions of cross-linked or grafted Pluronic copolymer chains in the micelle structure with increasing temperature. Transmission electron microscopy directly revealed that the shell cross-linked micelles were indeed produced by gold nanoparticles covalently clustered on the surface. These novel self-assembled organic/inorganic hybrid micelles would hold great potential for diagnostic and therapeutic applications.     

Preparation of pH- and thermo-sensitive chitosan-PNIPAAm core–shell nanoparticles and evaluation as drug carriers

Environmentally sensitive polysaccharide nanoparticles (NPs) were prepared by in situ polymerization of N-isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) micelles. First, CS was found to develop a cationic micelle-like structure in the acetic acid solution when its concentration was increased to above the critical micelle concentration, as evidenced by fluorescence and TEM. When the NIPAAm was polymerized in the CS micelle solution by using potassium persulfate as initiator, the produced PNIPAAm with anionic chain end(s) became hydrophobic, as long as the reaction temperature was above its phase transition temperature; and therefore it would diffuse into the hydrophobic core of the CS micelles, producing CS-PNIPAAm core–shell NPs. Increasing the feeding amount of NIPAAm increased the monomer conversion and therefore the particle size; yet it decreased the surface zeta potential. Moreover, the CS-PNIPAAm NPs were sensitive to both pH value and temperature. For the study of drug release properties, doxycycline hyclate was used as a model drug and loaded into the NPs at pH 4.5 and 25 °C. The result illustrated that these NPs had a continuous drug release behavior up to 1 week, depending on the pH value and temperature. In addition, enzyme or hydrogen peroxide capable of degrading CS shell was added in the solution to facilitate the drug release.     

A novel route for preparation of multifunctional polymeric nanocarriers for stimuli‐triggered drug release

Fluorescence‐incorporated, crosslinker‐free, pH‐ and thermoresponsive nanocarriers were prepared by the incorporation of drug molecules into the thermoresponsive nanocapsules, which composed of poly(N‐isopropylacrylamide) (PNIPAAm) with carboxylic acid end groups via temperature induced self‐assembling method. Well‐defined, pH‐responsive carboxylic acid group‐ended PNIPAAm homopolymer (HOOC? PNIPAAm? COOH) was synthesized by reversible addition fragmentation chain transfer polymerization with S,S′‐bis(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate (CMP) as a chain transfer agent. Rhodamine 6G (R6G), the model drug, was used for three kinds of application: First, the nanostructure fixing; second, the fluorescence‐labeling; and last, the controlled release modeling. The transmission electron microscope images showed the solution type dosing led to the encapsulation of drug molecules into the nanocarriers, while the powder‐type drug‐loading process significantly contributed to the structure preservation of nanocarriers. The controlled release behaviors with various pH values and temperatures were evaluated. These multifunctional nanocarriers have potential to be applied for the biomedical therapy by stimuli‐responsive controlled release. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 561–571     

Thermo/pH Dual Responsive Mixed‐Shell Polymeric Micelles Based on the Complementary Multiple Hydrogen Bonds for Drug Delivery

Thermo/pH dual responsive mixed‐shell polymeric micelles based on multiple hydrogen bonding were prepared by self‐assembly of diaminotriazine‐terminated poly(?‐caprolactone) (DAT‐PCL), uracil‐terminated methoxy poly(ethylene glycol) (MPEG‐U), and uracil‐terminated poly(N‐vinylcaprolactam) (PNVCL‐U) at room temperature. PCL acted as the core and MPEG/PNVCL as the mixed shell. Increasing the temperature, PNVCL collapsed and enclosed the PCL core, while MPEG penetrated through the PNVCL shell, thereby leading to the formation of MPEG channels on the micelles surface. The low cytotoxicity of the mixed micelles was confirmed by an MTT assay against BGC‐823 cells. Studies on the in vitro drug release showed that a much faster release rate was observed at pH 5.0 compared to physiological pH, owing to the dissociation of hydrogen bonds. Therefore, the mixed‐shell polymeric micelles would be very promising candidates in drug delivery systems.     

Thermoresponsive transport through ordered mesoporous silica/PNIPAAm copolymer membranes and microspheres

Thermosensitive inorganic-organic hybrid polymers and gels can be used for controlled molecular transport in a variety of applications that require robust, mechanically stable materials. Silica and poly(N-isopropylacrylamide) (PNIPAAm) precursors were copolymerized in the presence of surfactant supramolecular assemblies to form hybrid gels with ordered nanostructure. This method was less complicated and results in enhanced reversible transport properties compared to previous approaches noted herein. In this study, the thermoresponsive polymer, PNIPAAm, was incorporated into polymerizing silica networks using the coupling agent 3-methacryloxypropyltrimethoxysilane. The hydration transition of PNIPAAm associated with its lower critical solution temperature (LCST) in aqueous solution was retained in the hydrated silica matrices and was used to control the permeability of membranes and molecular release behavior of particles. This report presents new methods for formation of hybrid silica/PNIPAAm membranes and particles, characterization of these materials, and documentation of reversible molecular transport properties of these new hybrid materials.