N‐(2‐hydroxypropyl)methacrylamide‐based polymer conjugates with pH‐controlled activation of doxorubicin. I. New synthesis,physicochemical characterization and preliminary biological evaluation

New method of synthesis of water‐soluble polymer‐drug conjugates, exhibiting remarkable anticancer activity in mice models, has been developed. In the conjugates, an anticancer drug doxorubicin (DOX) is attached to a polymer carrier based on N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer via a hydrolytically labile hydrazone bond. New methacrylamide‐type comonomers, containing either hydrazide group or hydrazon of DOX, were used for copolymerization with HPMA. In contrast to the synthetic procedure described earlier the new method is simpler, cheaper, and results in a better‐defined conjugate structure. The conjugates are fairly stable in buffer at pH 7.4 (model of blood stream) but release DOX under mild acid conditions modeling the tumor microenvironment. The conjugates showed significant in vivo antitumor activity in treatment of T‐cell lymphoma EL‐4 bearing mice with up to 100% long‐term survivors. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Chitosan‐based interpolymeric pH‐responsive hydrogels for in vitro drug release

Two series of pH‐responsive biodegradable interpolymeric (IPN) hydrogels based on chitosan (Ch) and poly(vinyl alcohol) (PVA) were prepared for controlled drug release investigations. The first series was chemically crosslinked with different concentrations of glutaraldehyde and the second was crosslinked upon γ‐irradiation by different doses. The equilibrium swelling characteristics were investigated for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 as simulated gastric and intestinal fluids, respectively. 5‐Fluorouracil (FU) was entrapped in the hydrogels, as a model therapeutic agent, and the in vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4. FTIR, SEM, and X‐ray diffraction analyses were used to characterize and investigate the structural changes of the gels with the variation of the blend composition and crosslinker content before and after the drug loading. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2864–2874, 2007     

Synthesis and in vitro assessment of novel water‐soluble dextran‐docetaxel conjugates as potential pH sensitive system for tumor‐targeted delivery

Docetaxel is a potent taxane agent mostly used in breast, lung, and prostate cancers. Its low water solubility is the major drawback that leads to use of Tween 80 as surfactant and ethanol as solvent in market formulation. But, these excipients cause severe hypersensitivity reactions. In this study, docetaxel was conjugated to biocompatible polymer, dextran 70 kDa, via a pH sensitive linker to enhance solubility and diminish the need of surfactants. Folic acid was also conjugated to dextran to provide targeted delivery. Synthesized conjugates were examined for solubility, hemo‐compatibility, stability, and cytotoxicity on MCF‐7 and MDA‐MB‐231 cell lines. Results showed about 1200‐fold enhancement in water solubility by dextran and 280‐fold by dextran‐folate conjugation. Conjugates released the drug in a pH‐dependent manner and faster hydrolysis was observed in pH 5.4 than physiological pH 7.4. Docetaxel‐dextran conjugates showed proper hemo‐compatibility and presented greater cytotoxicity than docetaxel solution. Higher cytotoxicity was seen in folate conjugated samples and the final conjugates targeted by folate would be suitable novel substitutions for currently marketed formulation. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45457.     

Specific Spatial Localization of Actin and DNA in a Water/Water Microdroplet: Self‐Emergence of a Cell‐Like Structure

The effect of binary hydrophilic polymers on a pair of representative bio‐macromolecules in a living cell has been examined. The results showed that these bio‐macromolecules exhibited specific localization in cell‐sized droplets that were spontaneously formed through water/water microphase segregation under crowding conditions with coexisting polymers. In these experiments, a simple binary polymer system with poly(ethylene glycol) (PEG) and dextran (DEX) was used. Under the conditions of microphase segregation, DNA was entrapped within cell‐sized droplets rich in DEX. Similarly, F‐actin, linearly polymerized actin, was entrapped specifically within microdroplets rich in DEX, whereas G‐actin, a monomeric actin, was distributed evenly inside and outside these droplets. This study has been extended to a system with both F‐actin and DNA, and it was found that DNA molecules were localized separately from aligned F‐actin proteins to create microdomains inside microdroplets, reflecting the self‐emergence of a cellular morphology similar to a stage of cell division.     

Photopolymerized pH‐sensitive semi‐IPN: Synthesis,water uptake analysis,and preliminary drug release study

A series of pH‐sensitive semi‐IPN hydrogels, composed of varying amounts of monomer acrylic acid(AAc), crosslinker N,N′ methylene bisacrylamide, polymer cellulose acetate (CA) were synthesized via photoinitiated polymerization in dimethyl formamide (DMF) medium. The CA/P (AAc) hydrogels were characterized by FTIR, and TG analysis. The equilibrium water uptake data was used to determine various network parameters. For all the samples synthesized, the swelling exponent “n,” initial diffusion coefficient D and average diffusion coefficient D_ave were found to be in the range of 0.51–0.72, 3.16 to 7.14 × 10^?6 cm² min^?1 and 94.16–120.56 cm² min^?1, respectively. The hydrogel demonstrated fair pH‐dependent swelling behavior, with nearly 20% swelling in the medium of pH 1.0 and 615% in the medium of pH 7.4 at 37°C, respectively. The gel showed excellent swelling–deswelling cycles which were interpreted quantitatively by first order kinetic swelling and deswelling models. Finally, the preliminary insulin release study, carried out in the media of varying pH, observed almost 16% release of entrapped drug in the simulating gastric fluid (SGF) of pH 1.0 in first 2 h and nearly 51% in next 6 h in simulating intestinal fluid(SIF) of pH 7.4 at 37°C. POLYM. ENG. SCI., 53:2129–2140, 2013. © 2013 Society of Plastics Engineers     

Fabrication of size‐controllable mPEG‐decorated microparticles conjugating optically active ketoprofen based on self‐assembly of amphiphilic random copolymers

Novel size‐controllable mPEG‐decorated polymeric microparticles binding optically active ketoprofen were successfully fabricated based on chemoenzymatic synthesis and self‐assembly of amphiphilic random polymer–ketoprofen conjugates with mPEG and (S)‐ketoprofen as pendants. A series of mPEG₃₅₀‐ or mPEG₁₀₀₀‐functionalized amphiphilic random polymer–ketoprofen conjugates with drug loading capacity from 16.5% to 73.2% were easily prepared by combining enzymatic resolution with radical polymerization and characterized by Fourier Transform Infrared spectroscopy, ¹H‐NMR, and gel permeation chromatography. The formation of aggregates from the amphiphilic random polymer–ketoprofen conjugates was investigated by ultraviolet‐visible absorption spectra using pyrene as the guest molecule. Transmission electron microscopy measurement revealed that the self‐assemblies were well dispersed as spherical microparticles. The size of the self‐assemblies could be widely tuned by varying the length of mPEG chains and the content of ketoprofen in the synthetic polymer–ketoprofen conjugates, and a series of mPEG‐decorated (S)‐ketoprofen‐bound polymeric microparticles with average radius from 70 nm to 1.1 μm were obtained. The successful preparation of the microparticles containing (S)‐ketoprofen provided a new strategy for the design and fabrication of optically active drug delivery systems. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation of novel pH‐sensitive nanocomposites based on ionic‐liquid modified montmorillonite for colon specific drug delivery system

An ionic liquid monomer, 3‐methyl‐1‐[2‐(2‐methyl‐acryloxy)‐ethyl]‐imidazolium chloride, was synthesized through the quaternization of N‐methylimidazole and 2‐chloroethyl methacrylate. This ionic liquid monomer intercalated into the montmorillonite layers and subsequently copolymerized with methacrylic acid. The organic–inorganic composite was characterized by FTIR, XRD, SEM, and EDX to study their structure and properties. Naproxen as a model drug was entrapped in these pH‐sensitive positively charged nano carriers and the in vitro release profiles were established separately in both enzyme‐free simulated gastric and intestinal fluids (SGF, pH 1) and (SIF, pH 7.4) respectively. It was observed that the drug release percentages in SIF were higher; hence the prepared nanocomposite could be considered as a suitable carrier for colon specific drug delivery. POLYM. COMPOS., 182–187, 2016. © 2014 Society of Plastics Engineers     

Conjugates of poly(N‐isopropyl acrylamide‐co‐acrylic acid) with alanine monopeptide,dipeptide, and tripeptide

A random copolymer of N‐isopropyl acrylamide (NIPAAm) and acrylic acid (AAc) with an AAc content of 3.1 ± 0.19 mmol of carboxylic acid groups per gram of the copolymer and with a number‐average molecular weight of 1400 was synthesized by free‐radical polymerization with 2,2′‐azoisobutyronitrile in dimethylformamide. Then, monopeptide, dipeptide, and tripeptide (i.e., alanine) conjugates of this copolymer were prepared with their carboxyl‐end‐protected (with methyl ester hydrochloride) form of alanine, with a water‐soluble carbodiimide. Of the carboxylic acids, 93, 69, and 57% were conjugated (loaded) with alanine at the monopeptide, dipeptide, and tripeptide conjugation steps, respectively. The chemical structures of the copolymer and conjugates were analyzed by Fourier transform infrared and ¹H‐NMR, which revealed the conjugate formation. Amino acid conjugation caused significant decreases in the lower critical solution temperatures (LCST) of the copolymer, especially at pH 7.4. The LCST values of the dipeptide and tripeptide conjugates of poly(NIPAAm‐co‐AAc) at both pH 4.0 and 7.4 shifted to significantly higher temperatures. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2012–2019, 2003     

Synthesis and self‐assembly study of zwitterionic amphiphilic derivatives of chitosan

New zwitterionic derivatives of chitosan (CH) were synthesized through the Michael addition reaction of 1‐(3‐sulfopropyl)‐2‐vinylpyridine hydroxide (SPP) with primary amines of deacetylated CHs (with weight‐average molecular weights of 46 and 216 kDa) to obtain SPP‐substituted CHs. The hydrophilic derivatives were subsequently modified with 2.1, 4.6, and 9.7% of dodecyl groups [degree of substitution by dodecyl groups (DS_Dod)]. The SPP‐substituted CH derivatives were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography. Aqueous solutions of SPP‐substituted CH samples remained clear, independently of the pH (3.0 < pH < 12.0). The self‐association study of the amphiphilic derivatives was performed in aqueous buffered solution at pH 5.0 and 7.4, and the critical aggregation concentration values varied from 5.6 × 10^?3 to 0.02 g/L. The measurements of dynamic light scattering and ζ potentials showed that the self‐assembly behavior was dependent on the pH and DS_Dod. At pH 7.4, the measured ζ potentials were near zero, and colloidal stability was provided by the hydrated zwitterionic shell of the aggregates. Transmission electron microscopy revealed spherelike microsized particles of broad distribution. The amphiphilic SPP‐substituted CH samples were shown to be nontoxic with a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay performed with HeLa cells. The remarkable water solubility and nontoxicity displayed by the new SPP‐substituted CH derivatives showed promising properties for the design of CH‐based biomaterials and nanoparticles. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44176.     

An in vitro focus on doxorubicin hydrochloride delivery of novel pH‐responsive poly(2‐succinyloxyethylmethacrylate) and poly[(N‐4‐vinylbenzyl),N,N‐diethylamine] diblock copolymers

Novel pH‐responsive poly(2‐succinyloxyethylmethacrylate)‐b‐poly[(N‐4‐vinylbenzyl),N,N‐diethylamine] [poly(SEMA‐b‐VEA)] diblock copolymers were synthesized via reversible addition fragmentation transfer (RAFT) polymerization to investigate their self‐assembly micellar behavior. The self‐assembly behaviors of synthesized diblock copolymers with distinct molecular weights (labeled (1) to) were confirmed by ¹H NMR spectroscopy, TEM and dynamic light scattering measurements. Doxorubicin hydrochloride (DOX) loading capacity was evaluated, and the in vitro cytotoxicity effect of DOX‐loaded diblock copolymer was also studied by assessing the survival rate of the breast cancer cell line MCF‐7 with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results exhibited remarkable controlled release in the MTT assay. The DOX encapsulation efficiency was calculated to be 96.4%. The size and zeta potential of DOX‐loaded poly(SEMA‐b‐VEA) diblock copolymers were 204 nm and +5.7 mV at a pH of 7.4. DOX release values after 440 h at pH 7.4, 5.4 and 4 were 22.15%, 31.43% and 47.06%, respectively. The released values of DOX‐loaded poly(SEMA‐b‐VEA) and at pH 7.4 were 22.15%, 20.5% and 17.5%, respectively. Cell survival ratios were 18.9%, 23.16% and 16.92% after 72 h. Poly(SEMA‐b‐VEA) copolymers can be considered in nanomedicine applications due to their excellent pH‐responsive micellar behavior. © 2017 Society of Chemical Industry     

Diels–Alder‐based crosslinked self‐healing polyurethane/urea from polymeric methylene diphenyl diisocyanate

Crosslinked self‐healing polyurethane/urea based on a Diels–Alder reaction (C‐PMPU–DA) was synthesized from a multiple‐furan monomer and a commercial bismaleimide. The multiple‐furan monomer (PMPU–furan) was obtained from a functionalized prepolymer (polymeric MDI: PBA‐2000 = 2:1) by furfuryl amine. The structures of both the PMPU–furan and C‐PMPU–DA were characterized by attenuated total reflectance (ATR)–Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and ¹H‐NMR. The Diels–Alder bonds enabled C‐PMPU–DA thermal reversibility, which was investigated by ATR–FTIR spectroscopy, ¹H‐NMR, gel–solution–gel experiments, and viscosity tests. Meanwhile, the self‐healing properties of C‐PMPU–DA were also investigated by the recovery of the mechanical properties. The results showed that C‐PMPU–DA exhibited good thermal reversibility and self‐healing properties. C‐PMPU–DA exhibited thermosetting properties at room temperature, although it exhibited thermoplastic properties at higher temperatures and may find applications in self‐healing materials, recyclable materials, or removable materials. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40234.     

The diacetone acrylamide crosslinking reaction and its control of core‐shell polyacrylate latices at ambient temperature

Self crosslinkable core‐shell polyacrylate latices (PAs) cured at ambient temperature were synthesized by semicontinuous‐seeded emulsion polymerization with diacetone acrylamide (DAAM) and adipic dihydrazide (ADH) as crosslinkable monomers. The influences of DAAM monomer mass content, neutralizer, and curing temperature on the properties of self crosslinkable core‐shell latices and the keto‐hydrazide crosslinking were discussed. The spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), atomic force microscopy (AFM), transmission electron microscopy (TEM), and contact angle instruments were used to determine the structure and properties of PAs. The water evaporating rate during the film‐forming process of self crosslinkable core‐shell latices was also investigated. FTIR analyses demonstrate that the keto‐hydrazide crosslinking reaction does not occur in the latex environment but occurs at ambient temperature with the evaporation of water during the film‐forming process. The results of DSC show that the core‐shell crosslinkable PAs have two glass transition temperatures (T_g), and T_gs of crosslinked film are higher than that of non crosslinked fim. Moreover, the keto‐hydrazide reaction is found to be acid catalyzed and favored by the loss of water and the simultaneous decrease in pH arising from the evaporation of ammonia or amines during film‐forming process. Hence, in the volatile ammonia or amines neutralized latices, the latex pH value adjusted to 7–8, which not only ensure the crosslinkable latex with good storage stability but also obtain a coating film with excellent performances by introducing the keto‐hydrazine crosslinking reaction. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

pH‐sensitive hydroxyethyl starch–doxorubicin conjugates as antitumor prodrugs with enhanced anticancer efficacy

Doxorubicin (DOX) is a widely used chemotherapeutic drug for the treatment of several types of cancers, which has limitation in clinical applications because of severe heart toxicity. Herein, to reduce the fast clearance from the blood system and the severe systemic toxicity caused by the nonspecific protein adsorption, a pH‐sensitive drug delivery system with higher drug conjugated content was prepared by conjugating DOX onto hydroxyethyl starch (HES) with a pH‐sensitive hydrazone bond. In normal physiological environment, the release of DOX conjugated onto HES was slight which could be neglected without any side effect. However, in an acidic environment mimicking the tumor microenvironment, this pH‐sensitive hydrazone linkage provided a controlled and sustained release of DOX over a period of more than 3 days. The conjugates had good biocompatibility, long circulation, and lower cytotoxicity, which could efficiently be transferred into HeLa and HepG2 cells and release the conjugated drug. Based on these promising properties, these HES–DOX conjugates outline the significant potential for future biomedical application in the controlled release of antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42778.     

β‐cyclodextrin/poly(vinyl alcohol) hydrogels containing phenylpropionic acid and naphthylamine: dual pH‐sensitive release

Hydrogel composed of β‐cyclodextrin (β‐CD) and poly(vinyl alcohol) was prepared in a strong alkaline condition using epichlorohydrin as a crosslinker. Phenylpropionic acid (PPA) and naphthylamine (NA) were loaded in the cavities of β‐CD residues to endow the hydrogel with a dual pH‐sensitive characteristic. In release experiments using fluorescein isothiocyanate‐dextran (FITC‐dextran) as a dye, PPA/NA‐loaded hydrogel exhibited an extensive release not only in acidic conditions (e.g. pH 3.0) but also in alkaline conditions (e.g. pH 9.0). PPA and NA will be highly ionized at the alkaline and the acidic pH and they could promote swelling of the hydrogel, causing an extensive release at those pH values. However, the release was suppressed at mid pH values (e.g. pH 5.0 and pH 7.4), possibly due to the formation of salt bridges between PPA^? and NA⁺. In fact, the degree of swelling at mid pH was lower than that observed at strong acidic pH and alkaline pH. According to SEM images, the pore size and the texture compactness of hydrogels which had been subjected to swelling at different pH values could also account for the dual pH‐sensitive releases. The hydrogels exhibited dual pH sensitivities in terms of FITC‐dextran release and swelling. These hydrogels might be used as a pH‐sensitive vehicle for water‐soluble drugs. © 2013 Society of Chemical Industry     

β‐Galactosidase immobilization into poly(hydroxyethyl methacrylate) membrane and performance in a continuous system

The activity of β‐galactosidase immobilized into a poly(2‐hydroxyethyl methacrylate) (pHEMA) membrane increased from 1.5 to 10.8 U/g pHEMA upon increase in enzyme loading. The K_m values for the free and the entrapped enzyme were found to be 0.26 and 0.81 mM, respectively. The optimum reaction temperatures for the free and the entrapped β‐galactosidase were both found to be 50°C. Similarly, the optimum reaction pH was 7.5 for both the free and the entrapped enzyme. The immobilized β‐galactosidase was characterized in a continuous system during lactose hydrolysis and the operational inactivation rate constant (k_iop) of the entrapped enzyme was found to be 3.1 × 10⁻⁵ min⁻¹. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1367–1373, 1999     

Highly efficient adsorbent for organic dyes based on a temperature‐ and pH‐responsive multiblock polymer

The self‐assembly behavior of amphiphilic block copolymers in selective solutions has many applications in environmentally responsive polymer materials. In this article, we report on a new amphiphilic, temperature and pH dual‐responsive poly[2‐dimethylaminoethyl methacrylate‐co‐(methyl methacrylate)]‐b‐poly[poly(ethylene glycol) methacrylate] [P(DMAEMA‐co‐MMA)‐b‐PPEGMA], which was synthesized via reversible addition–fragmentation chain‐transfer polymerization. The structure, self‐assembly behaviors, and process of organic dye adsorption were characterized by ¹H‐NMR, ultraviolet–visible absorbance spectroscopy, and DLS measurements. P(DMAEMA‐co‐MMA)‐b‐PPEGMA was proven to be an outstanding adsorbent with excellent reversibility. Methyl red was released from the micelles as the pH value of the solution was adjusted to 4, and it could also be encapsulated again when the pH value was adjusted to 7.4 because of the sensitive pH‐responsive ability. It is promising that the triblock polymer had a positive effect on dye adsorption for environmental protection. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46626.     

Synthesis and characterization of PEG–PCL–PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer

Triblock copolymers of monomethoxy poly(ethylene glycol) (mPEG) and ε‐caprolactone (CL) were prepared with varying lengths of poly(ε‐caprolactone) (PCL) compositions and a fixed length of mPEG segment. The molecular characteristics of triblock copolymers were characterized by ¹H NMR, gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), and differential scanning calorimetry (DSC). These amphiphilic linear copolymers based on PCL hydrophobic chain and hydrophilic mPEG ending, which can self‐assemble into nanoscopic micelles with their hydrophobic cores, encapsulated doxorubicin (DOX) in an aqueous solution. The particle size of prepared micelles was around 40–92 nm. The DOX loading content and DOX loading efficiency were from 3.7–7.4% to 26–49%, respectively. DOX‐released profile was pH‐dependent and faster at pH 5.4 than pH 7.4. Additionally, the cytotoxicity of DOX‐loaded micelles was found to be similar with free DOX in drug‐resistant cells (MCF‐7/adr). The great amounts of DOX and fast uptake accumulated into the MCF‐7/adr cells from DOX‐loaded micelles suggest a potential application in cancer chemotherapy. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Thermotropic liquid crystalline poly (hydrazone–ether)s containing thiadiazole moiety in the main chain

A new homologous series of thermotropic liquid crystalline poly(hydrazone–ether)s based on the 1,3,4‐thiadiazole moiety in the main chain was synthesized by solution polycondensation of various diformyl‐α,ω‐diphenoxyalkanes with 2,5‐bis(mercaptoacetic hydrazide)‐1,3,4‐thiadiazole. The inherent viscosity of the polymers was prepared in the range of 0.39–0.76 dl g^?1. The phase behaviour of these polymers was studied by differential scanning calorimetry, optical polarizing microscopy using a heated stage, and thermogravimetric analysis. Almost all the polymers exhibited thermotropic liquid crystalline properties. In most cases, the mesophase extends to 335 °C, where thermal decomposition prevents further observation. Methoxy substituents on the benzene ring of these polymers lower the transition temperature significantly. Copyright © 2004 Society of Chemical Industry     

Dual Cross‐Linked Hydrogels with High Strength,Toughness, and Rapid Self‐Recovery Using Dynamic Metal–Ligand Interactions

A dual cross‐linking design principle enables access to hydrogels with high strength, toughness, fast self‐recovery, and robust fatigue resistant properties. Imidazole (IMZ) containing random poly(acrylamide‐co‐vinylimidazole) based hydrogels are synthesized in the presence of Ni²⁺ ions with low density of chemical cross‐linking. The IMZ‐Ni²⁺ metal–ligand cross‐links act as sacrificial motifs to effectively dissipate energy during mechanical loading of the hydrogel. The hydrogel mechanical properties can be tuned by varying the mol% of vinylimidazole (VIMZ) in the copolymer and by changing the VIMZ/Ni²⁺ ratio. The resultant metallogels under optimal conditions (15 mol% VIMZ and VIMZ/Ni²⁺ = 2:1) show the best mechanical properties such as high tensile strength (750 kPa) and elastic modulus (190 kPa), combined with high fracture energy (1580 J m^?2) and stretchability (800–900% strain). The hydrogels are pH responsive and the extent of energy dissipation can be drastically reduced by exposure to acidic pH. These hydrogels also exhibit excellent anti‐fatigue properties (complete recovery of dissipated energy within 10 min after ten successive loading–unloading cycles at 400% strain), high compressive strength without fracture (17 MPa at 96% strain), and self‐healing capability due to the reversible dissociation and re‐association of the metal ion mediated cross‐links.     

Synthesis of dextran‐metaxalone conjugates and study on their control drug release behaviors

Metaxalone (Met), a drug for treatment of pain and stiffness due to muscle injuries, was covalently linked to dextran via a chloroacetyl chloride spacer. The average molecular weights of dextran are 20,000 (D₂₀₀₀₀) and 40,000 (D₄₀₀₀₀), respectively, and the procedure of chemical modification for dextrans was conducted by a two‐step protocol: (1) synthesis of N‐chloroacetyl‐metaxalone; (2) synthesis of D₂₀₀₀₀‐Met and D₄₀₀₀₀‐Met. The controlled drug release studies were performed in buffer solutions with pH values of 1.1, 7.4, and 10.0. The results demonstrate that, under the same condition, the rate of release for D₂₀₀₀₀‐Met is slower than that of D₄₀₀₀₀‐Met, and more amount of Met can be detected releasing from polymer‐drug conjugate at the presence of α‐chymotrypsin in a buffer solution with pH = 8.0. It was also found that these novel polymer‐drug conjugates can effectively improve the Met's pharmacokinetics, and can increase its half‐life period. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008