Formation of a Polypseudorotaxane via Self‐Assembly of γ‐Cyclodextrin with Poly(N‐isopropylacrylamide)

A polypseudorotaxane (PPR) comprising γ‐cyclodextrin (γ‐CD) as host molecules and poly(N‐isopropylacrylamide) (PNIPAM) as a guest polymer is prepared via self‐assembly in aqueous solution. Due to the bulky pendant isopropylamide group, PNIPAM exhibits size‐selectivity toward self‐assembly with α‐, β‐, and γ‐CDs. It can fit into the cavity of γ‐CD to give rise to a PPR, but cannot pass through α‐CD and β‐CD under the same conditions. The ratio of the number of γ‐CD molecules to entrapped NIPAM repeat units is kept at 1:2.2 or 1:2.4, determined by ¹H NMR spectroscopy and TGA analysis, respectively, indicating that there are more than 2 but less than 3 NIPAM repeat units included by one γ‐CD molecule. This finding opens new avenues to PPR‐based supramolecular polymers to be used as solid, stimuli‐responsive materials.     

Synthesis of α‐Cyclodextrin‐Conjugated Poly(ε‐lysine)s and Their Inclusion Complexation Behavior

Novel functional polymers utilizing specific host/guest interactions were designed by introducing α‐CD host molecules into poly(ε‐lysine) chains as side groups. An interesting phase separation was observed as a result of the inclusion complexation between the polymeric host and 3‐(trimethylsilyl)propionic acid as a model guest in aqueous media. This water‐soluble polymeric host would be useful for various applications, particularly drug delivery, due to its biodegradability, low toxicity, and unique functionality represented as a complexation‐induced phase separation.     

Photoregulated Sol‐Gel Transition of Novel Azobenzene‐Functionalized Hydroxypropyl Methylcellulose and Its α‐Cyclodextrin Complexes

Summary: Novel azobenzene‐functionalized hydroxypropyl methylcellulose (AZO‐HPMC) polymers and their α‐cyclodextrin (α‐CD) complexes have been prepared. These polymers show interesting sol‐gel transition behavior in aqueous solutions. In the absence of α‐CD, the gelation temperature increases after UV irradiation, while in the presence of α‐CD, the gelation temperature decreases after UV irradiation. The difference in the gelation temperatures between the trans and cis samples of AZO‐HPMC opens a wide operating window for reversible regulation of the sol‐gel transition behavior by photoirradiation.

The UV‐induced cis/trans isomerism of azobenzene‐functionalized hydroxypropyl methylcellulose and its α‐cyclodextrin complexes.     

γ‐Cyclodextrin Derivatives Bearing Thymolphthalein Dyes in Their Secondary Hydroxyl Side as Guest‐Responsive Color Change Indicators

Two geometrically isomeric γ‐cyclodextrin derivatives with a thymolphthalein moiety in the secondary hydroxyl side were prepared as guest‐responsive color change indicators. The isomers exhibit a pH dependence of their absorption spectra and a remarkable change in the absorbance around 610 nm upon guest addition. One of the isomers formed complexes of 2 : 1, the other of 1 : 1 stoichiometry (host/guest).     

Dissociation behavior of poly(α‐hydroxy acrylic acid)

Dissociation behavior of poly(α‐hydroxy acrylic acid) (PHA) was investigated by potentiometric titration in the presence of NaCl and/or divalent metal chlorides. It was found that pH values of PHA aqueous solutions increased with time when the degree of dissociation, α, is high (α ≧ 0.5 for NaCl system) and decreased in the lower α region (α < 0.5 for NaCl). The increase of pH was attributed to lactone ring formation that occurs between a carboxyl group and a neighbor hydroxyl group upon protonation to the former, and the decrease of pH to an induction effect by lactone ring to −COOH group. The pH‐increasing process was analyzed by assuming it being of a first order to obtain a time constant. On the basis of time constant thus estimated and pKa values for divalent counterion systems, a correlation between counterion binding and lactone ring formation was discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1523–1531, 1999     

Paclitaxel‐Loaded β‐Cyclodextrin‐Modified Poly(Acrylic Acid) Nanoparticles through Multivalent Inclusion for Anticancer Therapy

A nanoassembled drug delivery system for anticancer treatment, formed by the host–guest interactions between paclitaxel (PTX) and β‐cyclodextrin (β‐CD) modified poly(acrylic acid) (PCDAA), is successfully prepared. After such design, the aqueous solubility of PTX is greatly increased from 0.34 to 36.02 μg mL^?1, and the obtained PCDAA‐PTX nanoparticles (PCDAA‐PTX NPs) exhibit a sustained PTX release behavior in vitro. In vitro cytotoxicity finds that PCDAA‐PTX NPs can accumulate significantly in tumor cells and remain the pharmacological activity of PTX. The in vivo real‐time biodistribution of PCDAA‐PTX NPs is investigated using near‐infrared fluorescence imaging, indicating that the PCDAA‐PTX NPs can effectively target to the tumor site by the enhanced permeability and retention effect in H22 tumor‐bearing mice. Through in vivo antitumor examination, PCDAA‐PTX NPs exhibit superior efficacy in impeding the tumor growth compared to the commercially available Taxol®.

     

Inclusion complex formation between α,γ‐cyclodextrins and organic–inorganic star‐shaped poly(ethylene glycol) from an octafunctional silsesquioxane core

A series of organic–inorganic star‐shaped poly(ethylene glycol)s from octafunctional silsesquioxane (POSS) cores were synthesized by allylation and hydrosilylation, and they were found to form crystalline inclusion complexes with α,γ‐cyclodextrins. The results from X‐ray diffraction, cross‐polarity/magic‐angle‐spinning ¹³C NMR, differential scanning calorimetry, and Fourier transform infrared suggested that a channel‐type structure was established in the inclusion complexes. The characterization results also revealed that the segments of poly(ethylene glycol) arms near the POSS cores were uncovered by the cyclodextrins, whereas the cyclodextrins were closely packed along the remaining portion of the poly(ethylene glycol) arms. Molecular dynamic simulation in a Dreiding force field with Cerius 2 software gave comparable results. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1173–1180, 2004     

Redox‐Responsive Hydrogel System Using the Molecular Recognition of β‐Cyclodextrin

Summary: We have successfully constructed a redox‐responsible hydrogel system by combination of β‐cyclodextrin (β‐CD), dodecyl‐modified poly(acrylic acid) [p(AA/C₁₂)], and a redox‐responsive guest, ferrocenecarboxylic acid (FCA). In the reduced state of FCA, the ternary mixture exhibited a gel‐like behavior, whereas, in its oxidized state, the mixture exhibited a sol behavior.

Conceptual illustration for the redox‐responsive hydrogel system.     

The effect of γ‐cyclodextrin addition in the self‐assembly behavior of pyrene labeled poly(acrylic) acid with different chain sizes

The interaction between poly(acrylic acid) polymers (PAA) of low‐ (2000 g/mol) and high‐ (450,000 g/mol) molecular weight (M_w) hydrophobically modified with pyrene (PAAMePy) and β‐ and γ‐cyclodextrins (β‐CD, γ‐CD) was investigated with fluorescent techniques. The interaction with β‐CD promotes little variation in the spectral and photophysical behavior of the polymer, whereas significant changes are observed upon addition of γ‐CD. The degree of inclusion (between the pyrene groups of the polymer and the cyclodextrins) is followed through the observation of the changes in the absorption, excitation (collected in the monomer and excimer emission regions) and emission (I_E/I_M ratio) spectra and from time‐resolved data. Within the studied range of γ‐CD concentration, the fluorescence decays of the long chain (high M_w) PAAMePy polymers were found tri‐exponential in the monomer and excimer emission regions in agreement with previous studies. In the case of the low M_w PAAMePy polymers, tri‐exponential decays were observed at the monomer and excimer emission wavelengths. However, when a γ‐CD concentration of 0.01 and 0.03 M is reached for, respectively, the low‐ and high‐labeled pyrene short chain (low M_w) polymers, the fluorescence decays in the excimer region become biexponential (two excimers) with no rising component, thus showing that all pyrene groups are encapsulated (and preassociated) into the γ‐CD cavity. In the case of the high M_w polymers, the addition of γ‐CD has been found to change the level of polymer interaction from pure intramolecular (water in the absence of cyclodextrin) to a coexistence of intra‐ with intermolecular interactions. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1402–1415, 2008     

Bioinspired Bioadhesive Polymers: Dopa‐Modified Poly(acrylic acid) Derivatives

The one‐step synthesis and characterization of novel bioinspired bioadhesive polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of certain gastropods, is reported. The novel polymers consist of combinations of either of two polyanhydride backbones and one of three amino acids, phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa‐grafted hydrophobic backbone polymers exhibit as much as 2.5× the fracture strength and 2.8× the tensile work of bioadhesion of a commercially available poly(acrylic acid) derivative as tested on live, excised, rat intestinal tissue.

     

Poly(acrylic acid)‐Modified Fe3O4 Microspheres for Magnetic‐Targeted and pH‐Triggered Anticancer Drug Delivery

Monodisperse poly(acrylic acid)‐modified Fe₃O₄ (PAA@Fe₃O₄) hybrid microspheres with dual responses (magnetic field and pH) were successfully fabricated. The PAA polymer was encapsulated into the inner cavity of Fe₃O₄ hollow spheres by a vacuum‐casting route and photo‐initiated polymerization. TEM images show that the samples consist of monodisperse porous spheres with a diameter around 200 nm. The Fe₃O₄ spheres, after modification with the PAA polymer, still possess enough space to hold guest molecules. We selected doxorubicin (DOX) as a model drug to investigate the drug loading and release behavior of as‐prepared composites. The release of DOX molecules was strongly dependent on the pH value due to the unique property of PAA. The HeLa cell‐uptake process of DOX‐loaded PAA@Fe₃O₄ was observed by confocal laser scanning microscopy (CLSM). After being incubated with HeLa cells under magnet magnetically guided conditions, the cytotoxtic effects of DOX‐loaded PAA@Fe₃O₄ increased. These results indicate that pH‐responsive magnetic PAA@Fe₃O₄ spheres have the potential to be used as anticancer drug carriers.     

Preparation and Aggregation of Polypseudorotaxane from Dendronized Poly(methacrylate)‐Poly(ethylene oxide) Diblock Copolymer and α‐Cyclodextrin

Summary: Dendronized poly(methacrylate)‐poly(ethylene oxide) (PDMA₅₈‐b‐PEO₄₅) formed as a stoichiometric inclusion complex with α‐cyclodextrin. The incorporation of the rodlike PDMA blocks produced no apparent change in the crystal structure, but its steric hindrance on the PEO chain resulted in lower yield as compared with the pure PEO. Moreover, the architectural transition from rod–coil to rod–rod led to a morphological change from spindly aggregates to rods in a binary solvent mixture of N,N‐dimethylformamide and water.

Synthesis and self‐assembly of the α‐cyclodextrin‐[dendronized poly(methacrylate)‐poly(ethylene oxide)] (α‐CD‐PDMA‐PEO) polypseudorotaxane (PR).     

Macromolecular Recognition by Polymer‐Carrying Cyclodextrins: Interaction of a Polymer Bearing Cyclodextrin Moieties with Poly(acrylamide)s Bearing Aromatic Side Chains

Summary: The interaction of a polymer bearing β‐cyclodextrin moieties (β‐CD polymer) with poly(acrylamide)s bearing aromatic side chains was investigated by viscometry to study the effect of collectivity (i.e., interactions at multi‐sites) in macromolecular recognition. The formation of inclusion complexes at multi‐sites caused a large difference in the size of interpolymer aggregates, even though the difference in association constants for complexation of native β‐CD with guest moieties was not very much large.

Conceptual illustration for interpolymer aggregates of β‐CD polymer with poly(acrylamide)s bearing naphthyl groups substituted on the (a) 1‐ and (b) 2‐positions (see Scheme 1 ).     

Preparation and characterization of poly(acrylic acid)‐iron rich smectite superabsorbent composites

A novel poly(acrylic acid)‐iron rich smectite (IRS) superabsorbent composite was synthesized by graft copolymerization reaction of acrylic acid (AA) in the presence of N,N‐methylenebisacrylamide (MBA) as a crosslinker. IRS was used to strengthen the hydrogel products in the polymerization process. Water absorbencies for these superabsorbent composites in water and saline solutions were investigated. IRS caused a reduced equilibrium swelling as low as 8–26%. However, grafted IRS particles resulted in improved gel strength as high as 66% compared to the IRS‐free sample. IRS modified superabsorbent hydrogel composites exhibited higher thermal stability compared to the IRS‐free sample. The pH dependent reversible swelling behavior of hydrogels was also investigated. It is found that the swelling process is pH dependent and reversible for synthesized superabsorbent. Superabsorbent hydrogel composites were characterized by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). FTIR spectroscopy was confirmed grafting of acrylic chains onto the surface of IRS particles. From the standpoint of these results, these strengthened and thermostabilized hydrogels may be considered as good candidates for a controlled release study and agricultural applications. Copyright © 2007 John Wiley & Sons, Ltd.     

Stimuli‐Triggered Sol–Gel Transitions of Polypeptides Derived from α‐Amino Acid N‐Carboxyanhydride (NCA) Polymerizations

The past decade has witnessed significantly increased interest in the development of smart polypeptide‐based organo‐ and hydrogel systems with stimuli responsiveness, especially those that exhibit sol–gel phase‐transition properties, with an anticipation of their utility in the construction of adaptive materials, sensor designs, and controlled release systems, among other applications. Such developments have been facilitated by dramatic progress in controlled polymerizations of α‐amino acid N‐carboxyanhydrides (NCAs), together with advanced orthogonal functionalization techniques, which have enabled economical and practical syntheses of well‐defined polypeptides and peptide hybrid polymeric materials. One‐dimensional stacking of polypeptides or peptide aggregations in the forms of certain ordered conformations, such as α helices and β sheets, in combination with further physical or chemical cross‐linking, result in the construction of three‐dimensional matrices of polypeptide gel systems. The macroscopic sol–gel transitions, resulting from the construction or deconstruction of gel networks and the conformational changes between secondary structures, can be triggered by external stimuli, including environmental factors, electromagnetic fields, and (bio)chemical species. Herein, the most recent advances in polypeptide gel systems are described, covering synthetic strategies, gelation mechanisms, and stimuli‐triggered sol–gel transitions, with the aim of demonstrating the relationships between chemical compositions, supramolecular structures, and responsive properties of polypeptide‐based organo‐ and hydrogels.     

Amphiphilic conetworks. IV. Poly(methacrylic acid)‐l‐polyisobutylene and poly(acrylic acid)‐l‐polyisobutylene based hydrogels prepared by two‐step polymer procedure. New pH responsive conetworks

This article describes the synthesis and characterization of new amphiphilic polymer conetworks containing hydrophilic poly(methacrylic acid) (PMAA) or poly(acrylic acid) (PAA) and hydrophobic polyisobutylene (PIB) chains. These conetworks were prepared by a two‐step polymer synthesis. In the first step, a cationic copolymer of isobutylene (IB) and 3‐isopropenyl‐α,α‐dimethylbenzyl isocyanate (IDI) was prepared. The isocyanate groups of the IB–IDI random copolymer were subsequently transformed in situ to methacrylate (MA) groups in reaction with 2‐hydroxyethyl methacrylate (HEMA). In the second step, the resulting MA‐multifunctional PIB‐based crosslinker, PIB(MA)_n, with an average functionality of approximately four methacrylic groups per chain, was copolymerized with methacrylic acid (MAA) or acrylic acid (AA) by radical mechanism in tetrahydrofuran giving rise to amphiphilic conetworks containing 31–79 mol % of MAA or 26–36 mol % of AA. The synthesized conetworks were characterized with solid‐state ¹³C‐NMR spectroscopy and differential scanning calorimetry. The amphiphilic nature of the conetworks was proven by swelling in both aqueous media with low and high pH and n‐heptane. The effect of varying pH on the swelling behavior of the synthesized conetworks is presented. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1284–1291, 2009     

Supramolecular Network Based on the Self‐Assembly of γ‐Cyclodextrin with Poly(ethylene glycol) and its Shape Memory Effect

A novel supramolecular network has been prepared based on the formation of inclusion complexes between γ‐cyclodextrin and poly(ethylene glycol), in which the PEG chains are interlocked by γ‐CD rings. This PEG/γ‐CD network exhibits good shape memory behavior because of the crosslinked structure. The crosslinked PEG/γ‐CD inclusion complexes and PEG crystallites account for the fixing phase and reversible phase, respectively. The characteristics of the materials have been investigated by ¹H NMR spectroscopy, XRD, DSC, DMA, viscosity tests, and swelling measurements.

     

Low‐Temperature Sol‐Gel Synthesis of Nanostructured Polymer/Titania Hybrid Films based on Custom‐Made Poly(3‐Alkoxy Thiophene)

A low‐temperature route to directly obtain polymer/titania hybrid films is presented. For this, a custom‐made poly(3‐alkoxy thiophene) was synthesized and used in a sol‐gel process together with an ethylene‐glycol‐modified titanate (EGMT) as a suitable titania precursor. The poly(3‐alkoxy thiophene) was designed to act as the structure‐directing agent for titanium dioxide through selective incorporation of the titania precursor. The nanostructured titania network, embedded in the polymer matrix, is examined with atomic force microscopy (AFM) and scanning electron microscopy (SEM) measurements. By means of the scattering technique grazing incidence wide‐angle X‐ray scattering (GIWAXS), a high degree of crystallinity of the polymer as well as successful transformation of the precursor into the rutile phase of titania is verified. UV/Vis measurements reveal an absorption behavior around 500 nm which is similar to poly(3‐hexyl thiophene), a commonly used polymer for photoelectronic applications, and in addition, the typical UV absorption behavior of rutile titania is observed.     

Sustained Drug Release by Thermoresponsive Sol–Gel Hybrid Hydrogels of Poly(N‐Isopropylacrylamide‐co‐3‐(Trimethoxysilyl)Propyl Methacrylate) Copolymers

Poly(N‐isopropylacrylamide‐co‐3‐(trimethoxysilyl)propyl methacrylate), P(NIPAAm‐co‐TMSPMA), copolymers with relatively high TMSPMA contents without insoluble fraction are successfully synthesized. Subsequent sol–gel reactions in both the absence and presence of tetraethyl orthosilicate lead to gels with high gel fractions. The resulting gels undergo gel collapse at 28.6–28.7 °C, i.e., below that of poly(N‐isopropylacrylamide) homopolymer of 34.3 °C. Unexpectedly, the theophylline‐loaded hybrid gels release the drug not only below but also above the gel collapse temperature (GCT) with considerable rates and released amounts of drug. Surprisingly, evaluation of the sustained release profiles by the Korsmeyer–Peppas equation indicates that the release occurs by Fickian diffusion above GCT, which can be attributed to the lack of significant drug–polymer interaction at such temperatures. These results can be widely applied for the design and utilization of TMSPMA‐based sol–gel polymer hybrids with desired release profiles of solutes below and above GCT for a variety of applications.