Synthesis and characterization of poly{N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid} hydrogels for drug delivery

A novel pH‐sensitive hydrogel system composed of itaconic acid (IA) and N‐[3‐(dimethylamino) propyl] methacrylamide was designed. This system was prepared by aqueous copolymerization with N,N‐methylene bisacrylamide as a chemical crosslinker. The chemical structure of the hydrogels was characterized by Fourier transform infrared (FTIR) spectroscopy. The microstructure and morphology of the hydrogels were evaluated by X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM study of hydrogels on higher magnification revealed a highly porous morphology with uniformly arranged pores ranging from 40 to 200 μm in size. XRD analysis revealed the amorphous nature of the hydrogels, and it was found that an increase in the IA content in the monomer feed greatly reduced the crystallinity of the hydrogels. Swelling experiments were carried out in buffer solutions at different pH values (1.2–10) at 37°C ± 1°C to investigate their pH‐dependent swelling behavior and dimensional stability. An increase in the acid part (IA) increased the swelling ratio of the hydrogels. Temperature‐sensitive swelling of the hydrogels was investigated at 20–70°C in simulated intestinal fluid. The hydrogels swelled at higher temperatures and shrank at lower temperatures. 5‐Aminosalicylic acid (5‐ASA) was selected as a model drug, and release experiments were carried out under simulated intestinal and gastric conditions. 5‐ASA release from the poly N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid‐80 (PDMAPMAIA‐80) hydrogel was found to follow non‐Fickian diffusion mechanism under gastric conditions, and a super case II transport mechanism was found under intestinal conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and release study of ibuprofen‐loaded porous matrices of a biodegradable poly(ester amide) derived from L‐alanine units

Scaffolds of a biodegradable poly(ester amide) constituted of L ‐alanine, sebacic acid, and 1,12‐dodecanediol units (abbreviated as PADAS) were prepared by the compression‐molding/particulate‐leaching method. The influence of the type, size, and percentage of salt on the scaffold porosity and morphology was evaluated. The thermal behavior and crystallinity were also studied for samples obtained under different processing conditions. PADAS scaffolds were not cytotoxic because they showed good cell viability and supported cell growth at a similar ratio to that observed for the biocompatible materials used as a reference. The use of PADAS scaffolds as a drug‐delivery system was also evaluated by the employment of ibuprofen, a drug with well known anti‐inflammatory effects. Different drug‐loading methods were considered, and their influence on the release in a Sörensen's medium was evaluated as well as the influence of the scaffold morphology. A sustained release of ibuprofen could be attained without the production of a negative effect on the cell viability. The release kinetics of samples loaded before melt processing was well described by the combined Higuchi/first‐order model. This allowed the estimation of the diffusion coefficients, which ranged between 3 × 10^?14 and 5 × 10^?13 m²/s. Samples loaded by immersion in ibuprofen solutions showed a rapid release that could be delayed by the addition of polycaprolactone to the immersion medium (i.e., the release rate decreased from 0.027 to 0.015 h^?1). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Optimizing the step‐by‐step forming processes for fabricating a poly(DL‐lactic‐co‐glycolic acid)‐sandwiched cell/hydrogel construct

A poly(DL ‐lactic‐co‐glycolic acid) (PLGA)‐sandwiched cell/fibrin construct was fabricated to overcome the weak mechanical properties of cell/hydrogel mixtures. This construct was formed with a step‐by‐step mold/extraction method to generate a middle smooth muscle layer of natural blood vessels. A desired three‐layer construct, as an integrated entity with optimized inner structures, was achieved by the control of the size of the molds, the concentration of the polymer systems, and the temperature of the extraction and polymerization processes. The constructs were fabricated with the following dimensions: length = 10–25 mm, diameter >2 mm, and wall thickness = 0.6–2 mm. Different microstructures in different layers of the sandwiched structure resulted in different functions. The pore structure in the inner PLGA and middle fibrin layers was beneficial for nutrient transference, whereas the solid structure without pores in the outmost surface of the outer PLGA layer could prevent fluid from leaking during in vitro culturing and in vivo implantation. This study showed that this can be a promising approach for the fabrication of synthetic‐polymer‐sandwiched viable cell/hydrogel constructs for wide potential application in complex organ manufacturing. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Comparison of the antibacterial activity of modified‐cotton with magainin I and LL‐37 with potential as wound‐dressings

Wounds are the ideal setting for the development of micro‐organisms, so it is often necessary to apply a dressing to control bacterial colonization. Cotton is commonly used in dressings, as it exhibits important hydrophilic characteristics such as high moisture and fluid retention properties, but it may provide a sustainable media for the development of micro‐organisms. In this way, the development of new strategies to provide cotton materials with lasting and effective antimicrobial properties is of the utmost importance. Consequently, here we described two processes to develop cotton‐dressings functionalized with antimicrobial peptides (AMPs) magainin I (MagI) and LL‐37, in order to give cotton‐dressings an antibacterial effect. The AMPs showed no cytotoxic effect against human fibroblasts so they are safe to contact with skin. In addition, the functionalized materials with either LL‐37 or MagI present an antimicrobial effect exhibiting inhibition ratios of 89% against Klebsiella pneumoniae and 58% against Staphylococcus aureus, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40997.     

Synthesis of PMMA‐PTHF‐PMMA and PMMA‐PTHF‐PST linear and star block copolymers

Combination of cationic, redox free radical, and thermal free radical polymerizations was performed to obtain linear and star polytetramethylene oxide (poly‐THF)‐polymethyl methacrylate (PMMA)/polystyrene (PSt) multiblock copolymers. Cationic polymerization of THF was initiated by the mixture of AgSbF₆ and bis(4,4′ bromo‐methyl benzoyl) peroxide (BBP) or bis (3,5,3′,5′ dibromomethyl benzoyl) peroxide (BDBP) at 20°C to obtain linear and star poly‐THF initiators with M_w varying from 7,500 to 59,000 Da. Poly‐THF samples with hydroxyl ends were used in the methyl methacrylate (MMA) polymerization in the presence of Ce(IV) salt at 40°C to obtain poly(THF‐b‐MMA) block copolymers containing the peroxide group in the middle. Poly(MMA‐b‐THF) linear and star block copolymers having the peroxide group in the chain were used in the polymerization of methyl methacrylate (MMA) and styrene (St) at 80°C to obtain PMMA‐b‐PTHF‐b‐PMMA and PMMA‐b‐PTHF‐b‐PSt linear and star multiblock copolymers. Polymers obtained were characterizated by GPC, FT‐IR, DSC, TGA, ¹H‐NMR, and ¹³C‐NMR techniques and the fractional precipitation method. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 219–226, 2004     

Polymeric calcium phosphate cements incorporated with poly‐γ‐glutamic acid: Comparative study of poly‐γ‐glutamic acid and citric acid

Polymeric calcium phosphate cements (PCPC) derived from biodegradable poly‐γ‐glutamic acid (γ‐PGA) were prepared in an attempt to improve the mechanical strength of calcium phosphate cement (CPC). The characteristics of the PCPCs were compared with those of cement incorporated with citric acid. The diametral tensile and compressive strengths of the CPC incorporated with γ‐PGA were significantly higher than that of cement incorporated with citric acid at equivalent concentrations (P < 0.05). The maximal diametral tensile and compressive strengths of the CPC incubated for 1 week in physiological saline solution were approximately 18.0 and 50.0 MPa, respectively. However, the initial setting time of the PCPC was slower than that of CPC incorporated with citric acid. The formation of ionic complexes between calcium ions and γ‐PGA was observed using FTIR spectroscopy. Hydroxyapatite (HA) formation was retarded by γ‐PGA incorporation according to scanning electronic microscopy (SEM) and powder X‐ray diffraction (XRD) observations. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis of a photoimmobilizable histidine polymer for surface modification

A novel photoreactive polymer with histidine polar groups was synthesized through the copolymerization of two types of methacrylic acid, one carrying histidine groups and the other carrying azidoaniline groups. The polymer was photoimmobilized on polyester disks for surface modification. The effect of the surface modification on the hydrophilic and biofouling properties was investigated. Static contact angle measurements showed that the polymeric surface was modified to be comparatively hydrophilic in the polymer‐immobilized region. Micropattern immobilization was carried out with a photolithographic method. Atomic force microscopy measurements showed that the polymer was formed on the disks in response to ultraviolet irradiation. Protein adsorption was reduced on the polymer‐immobilized regions, and in those regions, spreading and adhesion of mammalian cells were reduced in comparison with that in nonimmobilized regions. In conclusion, a novel histidine‐containing polymer was photoreactively immobilized on a conventional polymer surface, and it had reduced interaction with proteins and cells. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Cytotoxicity and cellular uptake evaluation of mitoxantrone‐loaded poly(lactic acid‐co‐lysine) arginine–glycine–aspartic acid nanoparticles

The purpose of this study was to evaluate the in vitro characteristics of poly(lactic acid‐co‐lysine) arginine–glycine–aspartic acid (PLA–PLL–RGD) nanoparticles (NPs) loaded with mitoxantrone. PLA–PLL–RGD NPs with a particle size of 200 nm were prepared with a modified emulsification solvent‐diffusion method. The encapsulation efficiency of the mitoxantrone‐loaded NPs was 85%. In vitro release experiments showed that the release of the drug was prolonged and sustained, and approximately 60.2% of the mitoxantrone was released in the first week. The released drug was integrated to achieve desired drug‐release profiles and still possessed bioactivity according to a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2h‐tetrazolium bromide assay, which indicated that mitoxantrone‐loaded NPs were more cytotoxic against Michigan Cancer Foundation 7 (MCF‐7) breast cancer cells than mitoxantrone. Furthermore, the association processes of NPs with MCF‐7 cells, including binding and effective internalization, were investigated in vitro. The cellular uptake of the NPs was qualitatively studied with confocal laser scanning microscopy and was confirmed with flow cytometry analysis. These experimental results indicated that PLA–PLL–RGD NPs could be used as drug carriers for mitoxantrone. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

The Photophysics of Polythiophene Nanoparticles for Biological Applications

In this work the photophysics of poly(3-hexylthiophene) nanoparticles (NPs) is investigated in the context of their biological applications. The NPs, made as colloidal suspensions in aqueous buffers, present a distinct absorption band in the low-energy region. On the basis of systematic analysis of absorption and transient absorption (TA) spectra taken under different pH conditions, this band is associated with charge-transfer states generated by the polarization of loosely bound polymer chains and originating from complexes formed with electron-withdrawing species. Importantly, the ground-state depletion of these states upon photoexcitation is active even on microsecond timescales, thus suggesting that they act as precursor states for long-living polarons; this could be beneficial for cellular stimulation. Preliminary transient absorption microscopy results for NPs internalized within the cells reveal the presence of long-living species, further substantiating their relevance in biointerfaces.     

Surface properties and biocompatibility of cellulose acetates

The article describes some properties of cellulose acetates (CAs) with different substitution degrees. The hydrophilic/hydrophobic properties, morphological aspects, and interface properties with red blood cells and platelets are affected by the substitution degree, synthesis conditions, history of the formed films from solutions in acetone/water nonsolvent/nonsolvent mixtures, and low pressure plasma treatment. The results obtained are useful in biomedical applications, including evaluation of bacterial adhesion onto surfaces, or utilization of CA for semipermeable membranes. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Development of redox‐mediated oxysilane sol–gel biosensors on carbon‐film electrode substrates

Three types of carbon‐film electrodes, made from electrical resistors with 1.5‐, 15‐, and 140‐Ω nominal resistances, were used to develop redox‐mediated sol–gel biosensors, and the results were compared with those from previously investigated 2‐Ω carbon‐film electrodes. Two different redox mediators, copper hexacyanoferrate and poly(neutral red), were deposited onto the carbon‐film electrodes, with the latter showing good electrochemical properties for electroanalytical applications, which were best on electrodes made from 15‐Ω carbon‐film resistors. It was not possible to deposit mediator film on the carbon‐film resistor electrodes of 140‐Ω nominal resistance. Glucose oxidase was immobilized on poly(neutral red) modified electrodes with sol–gel encapsulation from a mixture of 3‐glycidoxypropyltrimethoxysilane and methyltrimethoxysilane precursors at a volume ratio of 2 : 1. The best sensor electrochemical properties and response to glucose in model solution were found with electrodes constructed from 15‐Ω resistors, although the stability under the same conditions was better in the biosensors constructed with 2‐Ω nominal resistance electrodes. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis of 2‐hydroxypropyl dimethylbenzylammonium N,O‐(2‐carboxyethyl) chitosan chloride and its antibacterial activity

N,O‐(2‐carboxyethyl)chitosan (N,O‐2‐CEC) was prepared from chitosan with 3‐chloropropionic acid as modifying agent and NaOH as binding‐acid agent. 2‐Hydroxypropyl dimethylbenzylammonium N,O‐(2‐carboxyethyl) chitosan chloride (HPDMBA‐CEC) was obtained by the reaction of N,O‐2‐CEC with glycidyl dimethyl benzyl ammonium chloride (GDMBA) using NaOH as catalyst. The structures of chitosan derivatives were characterized by FTIR, ¹H NMR, and gel permeation chromatography. The antimicrobial activity of HPDMBA‐CEC was evaluated against a Gram‐negative bacterium Escherichia coli (E.coli) and a Gram‐positive bacterium Staphylococcus aureus (S. aureus). Compared with CTS, N,O‐2‐CEC, and HPDMBA‐CTS, HPDMBA‐CEC had much stronger antimicrobial activity, and this activity increased with increasing substitution degree of quaternary ammonium group (DQ). When the substitution degree of carboxyethylation (DS of CE) was 0.72 and DQ was 0.60, the minimum inhibitory concentrations (MICs) of HPDMBA‐CEC were 3.1 and 6.3 μg/mL against S. aureus and E. coli, respectively. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Microwave processing of starch‐based porous structures for tissue engineering scaffolds

A novel microwave (MW) processing technique was used to produce biodegradable scaffolds for tissue engineering from different types of starch‐based polymers. Potato, sweet potato, corn starch, and nonisolated amaranth and quinoa starch were used to produce porous structures. Water and glycerol were used as plasticizers for the different types of starch. Characterization of the pore morphology of the scaffolds was carried out with scanning electron microscopy. Three‐dimensional structures with variable porosity and pore size distribution were obtained with the MW foaming technique. The amount of remaining water in the scaffolds and their corresponding densities showed important variations among the different types of starch. Compressive mechanical properties were assessed by indentation tests, and a strong dependence of the indentation stress on the average pore size was found. Studies in simulated body fluid were used to assess the in vitro bioactivity, degradability, and surface topology evolution in the scaffolds. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1332–1339, 2007     

Preparation and evaluation of floating‐bioadhesive microparticles containing clarithromycin for the eradication of Helicobacter pylori

The development of a gastric floating‐bioadhesive drug delivery system to increase the efficacy of clarithromycin against Helicobacter pylori is described. Floating‐bioadhesive microparticles containing clarithromycin were prepared by a combined method of emulsification/evaporation and internal/ion gelation for the treatment of H. pylori infection. Ethylcellulose microspheres (EMs) were prepared by the dispersion of clarithromycin, ethylcellulose, and chitosan in dichloromethane and subsequent solvent evaporation. EMs were coated with alginate by the internal gelation process to obtain alginate–ethylcellulose microparticles (AEMs); then, AEMs were dispersed in a chitosan solution, and chitosan–alginate–ethylcellulose microparticles (CAEMs) were obtained by ion gelation to enhance the bioadhesive properties. The morphologies of EMs and CAEMs were investigated under optical and scanning electron microscopes. In vitro buoyancy and drug‐release testing confirmed the good floating and sustained‐release properties of CAEMs. About 74% of the CAEMs floated in an acetate buffer solution for 8 h, and 90% of the clarithromycin contained in the CAEMs was released within 8 h in a sustained manner. In vivo mucoadhesive testing showed that 61% of the CAEMs could be retained in the stomach for 4 h. Under a pretreatment with omeprazole, the clarithromycin concentration in gastric mucosa of the CAEM group was higher than that of the clarithromycin solution group. These results suggest that CAEMs might be a promising drug delivery system for the treatment of H. pylori infection. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 2226–2232, 2006     

Iodine bactericidal action adsorbed in 2‐vinylpyridine copolymer networks

In the present work, different kinds of porous copolymer networks based on 2‐vinylpyridine (2VP) and divinylbenzene (DVB) containing anchored iodine were prepared and evaluated for inactivating Escherichia coli in an aqueous medium. By using bacterial viability assays with E. coli (AB 1157, wild‐type), the iodine bactericidal effect was investigated at room temperature by elution through short columns filled with copolymer beads. Saline solutions containing bacterial cells at several contents (10² to 10⁷ cells/mL) were eluted. After each elution, cell content viability was determined by plating these suspensions on nutritive agar plates, incubating them at 37°C for 24 h, and counting as colony‐forming units (CFUs). It was verified that the networks containing anchored iodine were completely bactericidal within a few minutes. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 972–976, 2004     

Synthesis,exchange reactions,and biological activity of poly(8‐methacryloxyquinoline)

8‐Methacryloxyquinoline (MAQ) was prepared through the reaction of 8‐hydroxyquinoline with either methacryloyl chloride or methacrylic acid in the presence of triethylamine or N,N‐dicyclohexylcarbodiimide, respectively. MAQ was polymerized in dimethylformamide with 2,2‐azobisisobutyronitrile as the initiator. The reactions of the resulting polymers with hydroxyl and amino compounds were studied. The polymers were characterized with IR, ¹H‐NMR, and mass spectroscopy. Some of the synthesized polymers were tested for their antimicrobial activity against bacteria and fungi. Generally, all the polymers were effective against the tested microorganisms, but their growth‐inhibition effects varied. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation of temperature‐ and pH‐sensitive,stimuli‐responsive poly(N‐isopropylacrylamide‐co‐methacrylic acid) nanoparticles

The effects of the monomer ratio, surfactant, and crosslinker contents on the particle size and phase‐transition behavior of the copolymer poly(N‐isopropylacrylamide‐co‐methacrylic acid) (PNIPAAm–MAA) were investigated with Fourier transform infrared, differential scanning calorimetry, and dynamic laser scattering techniques. In addition to the thermoresponsive property of poly(N‐isopropylacrylamide), ionized methacrylic acid groups brought pH sensitivity to the PNIPAAm–MAA copolymer particles. The polymer particle size varied with the amounts of the monomer ratio, surfactant, and crosslinker. As the monomer ratio and crosslinker content increased and the amount of the surfactants decreased, the particle size increased. The influence of the crosslinker content on the particle size was less significant than the effect of the monomer ratio and surfactants. When the temperature increased, the particles tended to shrink and decreased in size to near or below 100 nm. Particle sizes at 20°C decreased to less than 100 nm with increased surfactant content. The control of the particle size within the 100‐nm range makes PNIPAAm–MAA copolymer particles useful for biomedical and heavy‐metal‐ion adsorption applications. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Polyphosphoester‐based paclitaxel complexes

We demonstrated a feasible approach for the preparation of a biodegradable, water soluble polyphosphoester based paclitaxel complex. Applying poly(hydroxyoxyethylene phosphate) which contains both a strong proton accepting P?O group and a proton donating P? OH group, paclitaxel has been physically immobilized onto the polymer via H‐bonding. The water soluble complex contained 16.7 wt % paclitaxel and more than 4000 times increased drug solubility was achieved. The polymer‐drug complex formed nanosized aggregates that were characterized by dynamic light scattering. Intravenous injection of poly(hydroxyoxyethylene phosphate) in rats at a dose of 1000 mg/kg did not induce any clinical signs or body weight gain reduction. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42772.     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.