Thermo- and pH-sensitive dendrimer derivatives with a shell of poly(N,N-dimethylaminoethyl methacrylate) and study of their controlled drug release behavior

Novel dendrimer derivatives combining the temperature- and pH-sensitivities are synthesized. At first, polyamidoamine (PAMAM) dendrimers with generations 1-5 are synthesized by the reaction of ethylenediamine with methyl acrylate, and then the dendrimers are acylated by chloroacetyl chloride to obtain PAMAM-Cl, which can act as a macroinitiator for further synthesizing functional dendrimers. For fulfilling this goal, the polymers consisting of a dendritic PAMAM core and poly(N,N-dimethylaminoethyl methacrylate) (PDMA) shell are synthesized by atom transfer radical polymerization (ATRP). Their macromolecular structures are characterized by FTIR, ¹H NMR, DSC and particle size analyses, and their aqueous solutions are inspected by UV spectroscopy for understanding their thermo- and pH-sensitivities. The results show that novel dendrimer derivatives exhibit clearly thermo- and pH-respondings in accordance with the change of the environment. Using chlorambucil (CLB) as a model drug, the behaviors of the controlled drug release from polymers with different average graft length of PDMA are studied. The results indicate that the rate of the drug release can be effectively controlled by the pH value.     

Synthesis and responsive behavior of poly(N,N-dimethylaminoethyl methacrylate) brushes grafted on silica nanoparticles and their quaternized derivatives

Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) was grafted onto the surface of silica nanoparticles via surface-initiated atom transfer radical polymerization to form temperature- and pH-responsive PDMAEMA brushes (silica-g-PDMAEMA). The resultant samples were characterized via ¹H NMR, transmission electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Their molecular weights and molecular weight distributions were determined by gel permeation chromatography analysis after silica content etching. The control of brush thickness and the responsive behavior were systematically investigated. Dynamic light scattering (DLS) results indicate that the brush thickness can be controlled by changing the polymerization time and the DMAEMA, initiator, and THF concentrations. According to DLS and zeta potential results, the lower critical solution temperature (LCST) of the PDMAEMA brushes shifts to a higher temperature with decreasing solution pH, which is attributed to the weak charge of the polyelectrolyte brushes. When the temperature is kept above the transition temperature, the silica-g-PDMAEMA nanoparticles aggregate into clusters and disaggregate during the cooling process. Moreover, with the heating/cooling step increasing, the aggregation and disaggregation temperatures are decreased. Meanwhile, when the molecular weight is increased from 13.6 × 10⁴ to 23.1 × 10⁴ g/mol, a decrease in the LCSTs at constant pH is observed. The related properties of the corresponding quaternized analog, poly{[2-(methacryloyloxy)ethyl] trimethylammonium iodide} (PMETAI) brushes, were also discussed. The hydrodynamic radius of the silica-g-PMETAI nanoparticles decreases with increasing ionic strength, and a salting-out/salting-in effect is observed when the ionic strength is adjusted using NaI instead of NaCl.     

Single-molecular hybrid nano-cylinders: Attaching polyhedral oligomeric silsesquioxane covalently to poly(glycidyl methacrylate) cylindrical brushes

We present the preparation of novel single-molecular hybrid nano-cylinders by covalently attaching a monothiol-functionalized polyhedral silsesquioxane (POSS-SH) to poly(glycidyl methacrylate) (PGMA) cylindrical brushes. Grafting of GMA from a long poly-initiator poly(2-(2-bromoisobutyryloxy)ethyl methacrylate) (PBIEM) via ATRP was first carried out. Gel permeation chromatography (GPC), ¹H NMR, dynamic light scattering (DLS), static light scattering (SLS) and atomic force microscopy (AFM) measurements confirmed the well-defined worm-like structures of the PGMA brushes. Then POSS-SH was covalently linked to PGMA brushes by reaction with about 19% of the epoxy groups. The successful preparation of the PGMA-POSS hybrid brush was demonstrated by Fourier-transform infrared spectroscopy (FTIR), DLS, SLS, energy dispersive X-ray spectroscopy (EDX) and thermogravimetric analysis (TGA) measurements. An increase of the length and diameter of the brushes was shown by AFM and non-stained transmission microscopy (TEM) measurements. Residual SiO₂ after pyrolysis of the PGMA-POSS hybrid brush in air displayed interesting cylindrical network structures.     

Influence of poly(acrylic acid) grafting density on switchable protein adsorption/desorption of poly(2-methyl-2-oxazoline)/poly(acrylic acid) mixed brushes

Poly(dopamine) is employed as an anchor to obtain a series of poly(acrylic acid) (PAA) and poly(2-methyl-2-oxazoline) (PMOXA) mixed brush coatings by sequential grafting to methods with PAA chains longer than PMOXA chains. Then, the prepared mixed brush coatings are rigorously characterized. The results show that the grafting density of PAA in mixed brushes could be well adjusted by changing the concentration of PAA solution used for the preparation of mixed brush coatings and the amounts of lysozyme adsorbed on PMOXA/PAA mixed brushes increase with increasing the grafting density of PAA chains while the desorption amounts decrease significantly when the grafting density of PAA is higher than one-half of PMOXA chains. When the grafting density of PAA is about one-half of PMOXA chains, the mixed brush could absorb high amounts of lysozyme (898.4 ng cm⁻²), and then more than 90% of adsorbed proteins could be released sharply by changing pH and ionic strength (I). © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48135.     

Effect of molecular weight and polymer concentration on the triple temperature/pH/ionic strength-sensitive behavior of poly(2-(dimethylamino)ethyl methacrylate)

Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) samples were synthesized via aqueous atom transfer radical polymerization with DP_n of 35, 151, 390, and 546 and dispersity of 1.13, 1.17, 1.20, and 1.18, respectively. All samples were exposed to temperature and pH variations at different concentration of polymer and salt (NaCl). Results indicated that cloud point (T_cl) can be controlled by changing DP_n, polymer concentration, and ionic strength of solution. According to results, T_cl of the PDMAEMA chains shifted to lower temperatures with increasing solution pH at all molecular weight ranges due to deprotonation of tertiary amine groups in polymer structure. However, higher molecular weight polymers were more sensitive to pH variation especially in alkaline media. Also, higher polymer concentration acted as driving force to decrease cloud point of samples and formation of aggregates that was more predominant for higher molecular weights at alkaline media. T_cl of PDMAEMA chains decreased with increasing ionic strength even at low pH values for low molecular weight polymers.     

Optical tweezers to measure the interaction between poly(acrylic acid) brushes

Optical tweezers are employed to measure the forces of interaction within single pairs of poly(acrylic acid) (PAA) grafted colloids with an extraordinary resolution of ±0.5 pN. Parameters varied are the concentration and valency of the counterions (KCl, CaCl₂) of the surrounding medium as well as its pH. The data are quantitatively described by a recently published model of Jusufi et al. [Colloid Polym Sci 2004; 282:910] for spherical polyelectrolyte brushes which takes into account the entropic effect of the counterions. For the scaling of the brush height a power law is found having an exponent of 0.25 ± 0.02 which ranges between the values expected for spherical and planar brushes. From the model the ionic concentration inside the brush is estimated in reasonable agreement with the literature.     

Mixed poly(methyl methacrylate)/poly(ethylene glycol) brushes: Study of switching behavior in selective solvent

The mixed polymer brushes composed of two incompatible polymers, poly(methyl methacrylate) and poly(ethylene glycol), were successfully synthesized via a sequential grafting to method, which was confirmed by water‐contact angle and ellipsometric measurements. The resulted mixed polymer brushes could undergo conformational rearrangements upon exposure to different selective solvents, and then the lateral segregation in nonselective solvent and perpendicular segregation in selective solvent happened. As a result, the mixed polymer brushes exhibited the ripple morphology and dimple morphology in corresponding solvent, respectively, and which led to changes in water‐contact angle and surface composition as a function of bulk composition of the mixed polymer brushes. Moreover, the switching properties as the surface composition, wettability and topographical images could occur in a controlled and reversible fashion. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Main-chain sulphur containing water soluble poly(N-isopropylacrylamide-co-N,N′-dimethylacrylamide sulphide) copolymers via interfacial polycondensation

Here, we report the first synthesis of water soluble poly(N-isopropylacrylamide-co-N,N′-dimethylacrylamide sulfide) copolymers via conventional interfacial polycondensation method using phase transfer catalyst (PTC). The effect of various kinds of PTC having different aliphatic chain length and counter ion were employed to examine the kinetics of polysulfide polymer formation. The reactivity ratios, determined employing extended Kelene–Tüdös method using feed composition obtained from ¹H NMR analysis, suggest that N-isopropylacrylamide (NIPAM) is more reactive than N,N′-dimethylacrylamide (DMA) in both mono- and di-sulfide polymers. Thermal transition behavior investigated by differential scanning calorimetry (DSC) demonstrated that as the sulphur rank of the sulfide main chain linkages increased, the flexibility of the polymers increased reflected by lower glass transition temperature (T_g) values. The thermal degradation behavior and the major degradation products have been characterized by thermogravimetric analysis (TGA) and electron-impact mass spectroscopy (EI-MS), respectively. Both the studies reveal that the degradation takes place due to weak-link scission of the polymeric main chain. Solubility in water and in most of the common organic solvents even after the sulphur rank increased from 1 to 2 in the main chain, is expected to render potential applications in biological field as well as in industry for these interesting new class of polymers.     

Synthesis by RAFT polymerization and properties of anionic cylindrical molecular brushes bearing poly(acrylic acid) side chains

RAFT polymerization of acrylic acid (AA) in the presence of low-molecular chain transfer agent (2-(butylthiocarbonothioylthio) propanoic acid and polyacrylate-based backbone bearing multiple butylthiocarbonothioylthio moieties is reported demonstrating successful synthesis of linear pAA with low polydispersity and anionic cylindrical molecular brushes, respectively. Twofold excess of butylthiocarbonothioylthio moieties attached to polyacrylate-based backbone over the initiator was optimal enabling to synthesize graft copolymers with rather low polydispersity (PDI 1.23–1.36) and reasonably high DP of pAA side chains (up to 25). Anionic cylindrical molecular brushes were characterized by SEC with triple detection, DLS, ¹H NMR spectroscopy, and potentiometric titration. Thermal transitions and thermal stability of the brush polymers bearing pAA side chains were determined by DSC and TGA.     

Poly(l-lactide) comb polymer brushes on the surface of clay layers

Poly(l-lactide) (PLLA) comb polymers on poly(hydroxyethyl methacrylate) (PHEMA) backbone were prepared on the surface of clay layers by a combination of in situ atom transfer radical polymerization (ATRP) and ring-opening polymerization. An ATRP initiator with a quaternary ammonium salt end group was intercalated into the interlayer spacing of clay. PHEMA polymer brushes on the surface of clay layers were prepared by in situ ATRP. PLLA comb polymers on PHEMA backbone were prepared by ring-opening polymerization. X-ray diffraction (XRD) and transmission electron microscopy (TEM) results showed that with the increase of comb chain length more and more exfoliated structure was created. Aggregation of wormlike comb polymer brushes on the surface of clay layers was observed by TEM. Differential scanning calorimeter (DSC) results indicated that both the melting points and glass transition temperatures of the comb polymer brushes increase with the increase of comb chain length. The equilibrium melting temperature of the comb polymer brush on the surface of clay layers is lower than cleaved polymer. An atomic force microscopy (AFM) image proves the formation of wormlike structure by cleaved comb polymers.     

Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide): synthesis, phase separation and particle formation

Grafting of poly(N-isopropylacrylamide) (PNIPAAm) having carboxylic groups at one end onto poly(allylamine) (PAH) in the presence of water soluble carbodiimide has yielded PAH-g-PNIPAAm copolymers with grafting ratios of 50, 29 and 18, respectively. These thermosensitive copolymers exhibit a lower critical solution temperature (LCST) at 34 °C at a temperature increase cycle regardless of their grafting ratios, a temperature identical to that of PNIPAAm-COOH oligomers. Temperature cycling reveals completely reversible polymer aggregation and dissolution above and below the LCST, respectively. Much smaller particle sizes are observed by scanning force microscopy and transmission electron microscopy compared to dynamic light scattering. A porous sphere model is suggested to depict the structure of the particles formed above the LCST, by which the dependence of the particle sizes on their grafting ratios is interpreted taking into account the surface tension and the spatial aggregation distance. Finally, to demonstrate the capability of the copolymers being used as thermosensitive polyelectrolytes, assembly onto multilayers is conducted and the increase of layer thickness is confirmed by small angle X-ray scattering and ellipsometry characterizations.     

A facile route to end-functionalized poly(N-isopropylacrylamide) brushes synthesized by surface-initiated SET-LRP

In this study, the facile synthesis of well defined, end-functionalized poly(N-isopropylacrylamide) [poly(NIPAM)] brushes was achieved by surface-initiated single-electron transfer living radical polymerization (SET-LRP). Surface-initiated SET-LRP of N-isopropylacrylamide in the presence of cysteamine chain transfer agent was conducted via Cu(0) generated in situ by the disproportionation of Cu(I) to Cu(0) and Cu(II) in N,N-dimethylformamide at 90 °C. Initially, silicon surfaces were modified with 2-bromopropionyl bromide (2-BPB). [Poly(NIPAM)] brushes with amine end-group were then synthesized via surface-initiated SET-LRP from the immobilized 2-BPB. Various characterization techniques including ellipsometry, grazing angle-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy and water contact-angle measurements were used to characterize the immobilization of 2-BPB on the silicon wafer and the subsequent polymer with amine end-group formation. The addition of free 2-BPB initiator was required for the formation of free polymer chains in solution. The free polymer chains were isolated and used to estimate the molecular weights and polydispersity index of chains attached to the surface. Although there are several chemicals methods for post-polymerization transformation of the halide chain end to amine groups, this study mainly provides a method for in situ functionalization of poly(NIPAM) brushes.     

Formation of poly(octadecyl acrylate) brushes on a silicon wafer surface

To introduce an ultrahydrophobic polymeric phase onto a silicon wafer, an initiator‐modified silicon wafer was prepared with 2‐bromopropionyl bromide and then surface‐initiated atom transfer radical polymerization of octadecyl acrylate was carried out from the initiator‐grafted silicon wafer using CuBr and N,N,N′,N″‐pentamethyldiethylenetriamine as catalyst precursors. The resultant poly(octadecyl acrylate) [poly(ODA)] brushes were characterized by ellipsometry, X‐ray photoelectron spectroscopy, grazing angle Fourier transform infrared spectroscopy, atomic force microscopy, gel permeation chromatography and water contact angle measurements. Wettability of the poly(ODA) brushes was found to depend on the surface coverage (Γ) and the root mean square roughness. The most hydrophobic surface (Γ = 25.35 mg m^?2 and root mean square roughness 11.9 nm) exhibited a water contact angle of 171.1 ± 0.2°. Copyright © 2011 Society of Chemical Industry     

Nanopatterns of poly(styrene-block-butyl acrylate) block copolymer brushes on the surfaces of exfoliated and intercalated clay layers

We report a study of poly(styrene-block-butyl acrylate) (PSBA) block copolymer brushes on the surfaces of intercalated and exfoliated silicate (clay) layers. The PSBA/clay nanocomposite was synthesized by in situ atom transfer radical polymerization (ATRP) from initiator moieties immobilized within the silicate galleries of the clay particles. Transmission electron microscopy (TEM) analysis showed the existence of both intercalated and exfoliated structures in the nanocomposite. Block copolymer brushes on the surface of exfoliated or intercalated clay layers were found to create nanopatterns after treatment in different solvents. For the block copolymer brushes after treatment in THF, uniform collapsed brush layers are observed. After treatment in acetone, a selective solvent for PBA, wormlike surface aggregates are observed. After treatment in methanol, a precipitant for both of the blocks, micelles as well as wormlike aggregates can be observed. Furthermore, the polymer brushes tend to aggregate together and change their nanopatterns at an elevated temperature.     

Synthesis and characterisation of stimuli-responsive poly(N,N′-diethylacrylamide) hydrogels

Stimuli-responsive poly(N,N′-diethylacrylamide) gels were prepared by free radical polymerisation in aqueous solution, using N,N-methylenebisacrylamide as crosslinking agent. The gels were compared with the corresponding poly(N-isopropylacrylamide)-based gels. In particular, the swelling ratio of both gel types including the effect of the crosslinker content, their swelling and deswelling kinetics, their permeability and finally their drug (insulin) storage and controlled release ability were compared. In spite of the similarity in the monomer/crosslinker ratio, the deswelling kinetics and the critical temperatures (ca. 30-32 °C in pure water), some differences could be observed. Compared to poly(N-isopropylacrylamide)-based gels, poly(N,N′-diethylacrylamide)-based gels show a broader phase transition temperature interval, a more pronounced dependency of the swelling ratio on the crosslinker content, slower reswelling kinetics, a higher ingress percentage for dextran standards ranging from 5 to 70 kD, but lower ingress percentages for proteins (BSA, insulin) and much faster drug (insulin) release kinetics. While a non-linear release kinetic was observed in the case of the poly(N-isopropylacraylamide)-based gels both in water and in PBS (phosphate buffered saline), this was not the case for the poly(N,N′-diethylacrylamide)-based gels.     

Comparison of the phase behaviour of the liquid-crystalline polymer/poly(methyl methacrylate) and poly(vinyl acetate)/poly(methyl methacrylate) blends

The phase behaviour of blends of a liquid-crystalline polymer (LCP) and poly(methyl methacrylate) (PMMA), as well as the phase state of blends of PMMA and poly(vinyl acetate) (PVA) has been investigated using light scattering and phase-contrast optical microscopy. The blends of LCP and PMMA have been obtained by coagulation from ternary solutions. The cloud point curves were determined. It was established that both pairs demix upon heating, ie have an LCST. In the region of intermediate composition, the phase separation proceeds according to a spinodal mechanism; however for LCP/PMMA blends, the decomposition proceeds according to a non-linear regime from the very onset. In the region of small amounts of LCP, the phase separation follows a mechanism of nucleation and growth. For PMMA/PVA blends, the spinodal decomposition proceeds according to a linear regime, in spite of the molecular mobility that PVA chains develop at lower temperatures. Only after prolonged heat treatment does the process transit to a non-linear regime. The data show a similarity between the phase behaviour of blends of liquid-crystalline and of flexible amorphous polymers. The distinction consists of the absence of a linear regime of decomposition for LCP-PMMA blends. © 1999 Society of Chemical Industry     

Self-reorganization of mixed poly(methyl methacrylate)/polystyrene brushes on planar silica substrates in response to combined selective solvent treatments and thermal annealing

This article reports reversible changes in surface morphology and surface wettability of mixed poly(methyl methacrylate) (PMMA)/polystyrene (PS) brushes with PS M_n slightly lower than that of PMMA in response to combined selective solvent treatments and thermal annealing. The mixed brushes were synthesized from asymmetric difunctional initiator-terminated monolayers by controlled radical polymerizations. Two sets of experiments were performed. The first set involved treating the samples with glacial acetic acid (AA), a selective solvent for PMMA, followed by treatment with cyclohexane, a selective solvent for PS, or thermal annealing. The surfaces were rough and composed of relatively ordered nanodomains after AA treatment. Subsequent cyclohexane treatment or thermal annealing made the surfaces flattened and surface analysis indicated that the outermost layers were occupied by PS. The second set of experiments involved treating the samples with cyclohexane or thermal annealing, followed by AA treatment. The surfaces were smooth after cyclohexane treatment or thermal annealing and became very rough in the subsequent AA treatment. The nanodomains formed in AA treatment were speculated to be micelles with PS forming the core shielded by PMMA chains.     

Crosslinked poly[acryloylN,N,-bis(2,2-dimethoxyethyl) amine] and crosslinked poly[acryloylmorpholine/acryloyl N,N,-bis(2,2-dimethoxyethyl) amine] gel networks and their application to the immobilization of β-d-glucosidase

The synthesis and homopolymerization of acryloyl N,N,-bis(2,2-dimethoxyethyl)amine is described. Gel networks were obtained by copolymerization of acryloyl N,N,-bis(2,2-dimethoxyethyl)amine and N,N,′-methylenediacrylamide (molar ratio 8:1) and by copolymerization of acryloyl morpholine, acryloyl N,N,-bis(2,2-dimethoxyethyl)amine and N,N,′-methylenediacrylamide (molar ratio 8:2:1). Following treatment of the gel networks with tartaric dihydrazide in dilute hydrochloric acid and subsequent activation with nitrous acid, conjugates of β-d-glucosidase were prepared. In both cases the immobilized enzyme was more resistant to heat denaturation than the native enzyme in solution. The nature of the polymer-enzyme linkage is discussed with reference to studies on the model compound phenylacetyl N,N-bis(2,2-dimethoxyethyl)amine.     

Studies of adsorption of alkaline trypsin by poly(methacrylic acid) brushes on chitosan membranes

Poly(methacrylic acid)‐grafted chitosan membranes (chitosan‐g‐poly(MAA)) were prepared in two sequential steps: in the first step, chitosan membranes were prepared by phase‐inversion technique and then epichlorohydrin was used as crosslinking agent to increase its chemical stability in acidic media; in the second step, the graftcopolymerization of methacrylic acid onto the chitosan membranes was initiated by ammonium persulfate (APS) under nitrogen atmosphere. The chitosan‐g‐poly(MAA) membranes were first used as an ion‐exchange support for adsorption of trypsin from aqueous solution. The influence of pH, equilibrium time, ionic strength, and initial trypsin concentration on the adsorption capacity of the chitosan‐g‐poly(MAA) membranes have been investigated in a batch system. Maximum trypsin adsorption onto chitosan‐g‐poly(MAA) membrane was found to be 92.86 mg mL^?1 at pH 7.0. The experimental equilibrium data obtained for trypsin adsorption onto chitosan‐g‐poly(MAA) membranes fitted well to the Langmuir isotherm model. The adsorption data was analyzed using the first‐ and second‐order kinetic models, and the experimental data was well described by the second‐order equation. More than 97% of the adsorbed trypsin was desorbed using glutamic acid solution (0.5M, pH 4.0). In addition, the chitosan‐g‐ poly(MAA) membrane prepared in this work showed promising potential for various biotechnological applications. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Optically active poly[thio-1-(N,N-diethylaminomethyl) ethylene]

Poly[thio-1-(N,N-diethylaminomethyl) ethylene] [poly(TDAE)] of different optical purities were prepared by stereoelective polymerization of racemic N,N-diethyl-N-(thiirane-2-ylmethyl) amine (TDAE) using a (1:1) $\text{ZnEt}{}_2\text{R}$ (?) 3,3-dimethyl 1,2-butanediol (R(?)DMBD) chiral initiator system. Optically enriched TDAE samples were isolated as residual monomers. These monomers were thermally polymerized to give optically active poly(TDAE) with randomly distributed R and S repeat units in various proportions. The configuration of the enantiomer preferentially incorporated into growing chains during the stereoelective polymerization was determined as R on the basis of the presence of a positive Cotton effect at 260 nm in the c.d. spectrum of residual monomers. This configuration agrees well with the known homosteric character of the $\text{ZnEt}{}_2\text{(?)}\text{DMBD}$ initiator system. ¹³C n.m.r. spectra of the different optically active poly(TDAE) samples and those of more or less stereoregular racemic ones were compared. It was found that the carbon atom of the main chain methine group is the only one which is stereosensitive. Observed triad effects were used to determine the degree of isotacticity of optically active poly(TDAE)s prepared by thermal polymerization of partly enriched monomers. The stereoelectivity of the initiator system and the optical activity of optically pure TDAE and poly(TDAE) were deduced. Side-chain nitrogen atoms did not show any competitive effect with sulphur atoms in the coordination process to the chiral initiator system.