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In this study, pH-responsive hydrogels, synthesized by the coupling reaction of polyacrylic acid and catechin, are proposed as carriers of oxidable drugs toward the GI tract. The presence of polyphenolic moieties in the network gives the polymers properties suitable for the release of unstable drugs in oxidative conditions. The characterization of the hydrogels is obtained by means of morphological and physico-chemical analyses, antioxidant assays and evaluation of the swelling behavior in media simulating the gastric (pH 1.0) and the intestinal (pH 7.4) tracts. The hydrogels are tested as pH-responsive carriers in in vitro release studies of folic acid and thiamine, two model drugs easily degraded by oxidative conditions simulated by UV irradiation and t-butyl hydroperoxide treatment, respectively. Results show that catechin-based carriers are able to control the release of drugs at different pH values, giving a remarkable improvement in the stability of the therapeutics. [ABSTRACT FROM AUTHOR]

Novel molecularly imprinted polymers (MIPs) suitable for the electroresponsive release of diclofenac were synthesized by precipitation polymerization in the presence of carbon nanotubes (CNTs). Both conventional and electroresponsive imprinted polymers were synthesized with methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the crosslinker. Preliminary experiments were performed to fully characterize the conventional MIPs and composite materials in terms of their morphological properties, recognition behavior, and electric resistivity. In vitro release experiments were performed in aqueous media to elucidate the ability of the MIPs and spherical imprinted polymers doped with CNTs to release the loaded template in a sustained manner over time in comparison to the that of the corresponding nonimprinted materials. Furthermore, a 20-V direct-current voltage was applied through the releasing media to evaluate how the electric field influenced the drug release to demonstrate the suitability of the proposed macromolecular system as an electroresponsive drug-delivery device. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 829-834, 2013 [ABSTRACT FROM AUTHOR]

Thermo-responsive polysaccharidic hydrogels were designed and synthesized by a free radical induced grafting procedure. Chitosan was chosen as biopolymer to impart biocompatibility and biodegradability to the macromolecular systems, while N-isopropylacrylamide (NIPAAm) was selected as co-monomer responsive for the thermo-sensitive properties. Ammonium persulfate was the initiator system and different polymeric networks have been synthesized by modulating the amount of NIPAAm in the polymerization feed. The resulting hydrogels were proposed as drug delivery devices and their performance was evaluated by using Diclofenac sodium salt as a model drug. Hydrogels were carefully characterized by FT-IR spectrophotometry, calorimetric analyses and swelling behavior in a temperature range of 15-45°C. Finally, to verify the suitability of these hydrogels as thermo-responsive devices, the drug release profiles were studied performing in vitro experiments around the swelling-shrinking transition temperatures of the macromolecular systems. [ABSTRACT FROM AUTHOR]

Context: Flavonoids preservation and release. Objective: Synthesis of a polymeric material able to prevent thermal and photo degradation of a flavonoid model compound, such as (+)-catechin, and suitable for a controlled/sustained delivery of this molecule in gastro-intestinal simulating fluids. Materials and methods: Methacrylic acid (MAA) was grafted onto poly( N-vinyl-pyrrolidone) (PVP) by a free radical grafting procedure involving a single-step reaction at room temperature. For this purpose, hydrogen peroxide/ascorbic acid redox pair was employed as water-soluble and biocompatible initiator system. Results and discussion: FT-IR spectra confirmed the insertion of MAA onto the polymeric chain. Stability studies, performed under various conditions, such as freeze-thaw cycles, exposure to strong light, thermal stability studies under constant humidity and with light protection at different temperatures, showed the preservative properties of the polymeric material towards flavonoids. Furthermore, the biocompatibility was highlighted by Hen's Egg Test-Chorioallantoic Membrane assay and in vitro release studies demonstrated the possibility to employ PVP-MAA copolymer as a device for gastro-intestinal release of flavonoids. Conclusion: The coupling of good preservative properties together with biocompatibility and the usefulness as carrier in controlled release make this kind of material very interesting from an industrial point of view for different applications in food, pharmaceutical, and cosmetic fields. [ABSTRACT FROM AUTHOR]

Objectives In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray-drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro. Methods Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated. Key findings Microparticles were positively charged with a mean size of 4.88 ± 0.3 μm. Microspheres were able to incorporate both RFP and ISN: encapsulation efficiency was 51 ± 6% and 22 ± 1%, respectively. X-ray diffraction study showed a new extensive and flattened diffraction peak providing evidence that the drugs were dispersed into the microparticles. Differential scanning calorimetry analysis confirmed effective interactions between gelatin and drug molecules by the presence of new transition peaks. Fifty-nine per cent of used microparticles were aerosolised. In-vitro toxicity studies on A549 alveolar basal epithelial cells showed that microparticles decreased cytotoxicity in comparison with the RFP solution. Laser scanning confocal microscopy observation confirmed that fluorescent probes delivered by microparticles are efficiently internalised in A549 cells. Conclusions Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery. [ABSTRACT FROM AUTHOR]

Native gelatin, N, N′-ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations. [ABSTRACT FROM AUTHOR]

Multi-walled carbon nanotubes were chemically functionalized with methacrylic acid and methacrylated bovine serum albumin by free radical grafting reaction to obtain novel nanocomposites. The nanotubes were synthesized by aerosol-assisted chemical vapor deposition, and then the monomers were directly grafted by the action of hydrogen peroxide/ascorbic acid redox pair which allows operating in water-compatible and eco-friendly environment without the generation of any toxic reaction by-product. A multi-technique approach was used to evaluate the effectiveness of the grafting process employing Fourier transform infrared, Raman, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, and thermogravimetric analyses. Considering the high importance of methacrylate polymers and bovine serum albumin, the proposed nanocomposites could be of great applicability in biomedical and pharmaceutical fields. [ABSTRACT FROM AUTHOR]

The aim of this study was to synthesize a new antibacterial and chelating biopolymer and to evaluate its germicidal activity and its ability in metal ions removal from aqueous solutions. The material was prepared via esterification of hemp with 2-benzyl-4-chlorophenol, a germicide agent, that was covalently coupled to cellulose backbone of hydrophilic fibers by a heterogeneous synthesis, to produce a functionalized biopolymer with a satisfactory degree of substitution. The obtained biopolymer was characterized by infrared spectroscopy and differential scanning calorimetry. Its antibacterial activity in inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth in Petri dishes, was evaluated. The results suggested that this biomaterial possesses an excellent in vitro antibacterial activity and so it can be efficiently employed in biomedical fields to ensure a protection against contaminations. On the other hand, the functionalized biopolymer interacts with metal ions thanks to its chelating functional groups. The absorption capacity for a selected metal ion such as Cd(II), was investigated in aqueous solution at pH 0.65, 4.1 and 7.0 by optical emission spectroscopy. This study showed that the new system is very effective in chelating cadmium ions showing the maximum efficiency at pH 4.1. This feature makes the synthesized biomaterial a potential candidate for metal ions removal. Graphical Abstract: [Figure not available: see fulltext.]Hemp fiber ( Cannabis sativa L.) derivatives with antibacterial and chelating properties. Roberta Cassano, Sonia Trombino, Teresa Ferrarelli, Fiore Pasquale Nicoletta, Maria Vittoria Mauro, Cristina Giraldi, Nevio Picci [ABSTRACT FROM AUTHOR]

The aim of this work was to synthesize collagen α-tocopherulate for topical treatments. Collagen is a natural polymer largely applied to enhance wound repair, and α-tocopherol is a known antioxidant used for the treatment of various skin diseases. Linking the two through covalent bonds could improve α-tocopherol transport and metabolic stability, reduce the rate of degradation, and ensure a longer persistence than free antioxidant. The new biopolymer was prepared by a solid-phase synthesis employing a carboxypolystyrene resin. Its antioxidant activity in rat liver microsomal membranes was also evaluated. The obtained collagen-based biomaterial represents a new prodrug of α-tocopherol that could be used for various biomedical applications. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Purpose: A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). Methods: The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated. Results: Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells. Conclusion: The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy. [ABSTRACT FROM AUTHOR]

A novel flavonoid-polysaccharide conjugate was synthesized by free radical grafting of quercetin on starch. The covalent insertion of quercetin in the polymeric chain was confirmed by FT-IR, DSC and fluorescence analyses, while an estimation of the amount of quercetin bound per g of polymer was obtained by the Folin-Ciocalteu assay. The conjugate shows improved UV stability and retains the antioxidant properties of free quercetin, such as scavenging activity towards free radicals (DPPH and peroxynitrite); inhibition of the free radical formation (peroxidation of linoleic acid) and total antioxidant activity. The conjugate also prevented drug degradation and shows potential health functionality in the treatment of Alzheimer disease, diabetes and as skin-whitening agent. [ABSTRACT FROM AUTHOR]

Objectives A novel and simple method to synthesize antitubercular-protein conjugate by solid phase synthesis was developed employing a carboxypolystyrene resin. The aim was to covalently bind a drug with antitubercular activity, isoniazid, to a biomacromolecule, gelatin, widely used in the pharmaceutical, cosmetic and food industry. Methods Calorimetric and 1H NMR analyses were performed to verify the bond formation between the antitubercular drug and gelatin. After absorption isoniazid delivers toxic metabolites and so an oxidation test with tert-butyl hydroperoxide was performed to assess the amount of toxic metabolites released from the prodrug (gelatin linked to isoniazid), compared with isoniazid itself. Key findings Spectrophotometric analysis revealed that the protein derivative was an excellent isoniazid prodrug since there was a 40% reduction in release of toxic metabolites (isonicotinic acid) by the prodrug. The results clearly showed that antitubercular moieties, covalently linked to a natural polymer, allowed the introduction of peculiar features for specific pharmaceutical applications into the macromolecule. In addition, antitubercular activity of the new polymer was determined by Middlebrook 7H11 medium against Mycobacterium tuberculosis complex. Conclusions The new isoniazid-gelatin conjugate showed significant antitubercular activity and for this reason should be useful as an efficacious tool in the treatment of tuberculosis. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to develop small microspheres for delivering antimycobacterial drugs to infected host macrophages. Rifampicin-based microparticles were prepared. The drug was covalently linked to acrylic moieties to obtain a polymerizable derivative for the preparation of materials useful as drug delivery systems that then were loaded with isoniazid acting in synergy with rifampicin. Their antitubercular activity was determined in vitro. Fourier transform infrared spectroscopy confirmed hydrogel structure. Morphological analysis showed microparticles with spherical shape and homogeneous surface. In vitro release studies were performed in media simulating physiologic pH (7.4) and endosomal of alveolar macrophages pH (5.2). A similar amount of isoniazid was delivered within the first 6 h at both pHs, while a smaller amount of the drug was delivered at pH 7.4 in the last phase of the study. In vitro antitubercular activity showed a behavior comparable to that of rifampicin and isoniazid free. Bioactive swelling matrices, showing a high swelling degree into a medium miming intra alveolar environment, were obtained. They could be applied for their antitubercular activity. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012. [ABSTRACT FROM AUTHOR]

Novel stimuli-responsive hydrophilic microspheres were prepared by free radical polymerization of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MA), as hydrophilic monomers, and N-isopropylacrylamide (NIPAAm) and N, N′-ethylenebisacrylamide (EBA), as thermo-sensitive monomer and crosslinker, respectively. Hydrophilic comonomers were introduced in the macromolecular network to synthesize materials with tunable thermal behavior. In addition, by introducing in the polymerization feed both a hydrophilic and a pH-sensitive monomer, such as MA, dual stimuli-responsive (pH and temperature) hydrogels were synthesized. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and the shape of hydrogels was found to strictly depend on the concentration of monomers in the polymerization feed. Thermal analyses showed negative thermo-responsive behavior with pronounced water affinity of microspheres at a temperature lower than lower critical solution temperature (LCST). In our experiment, the LCST values of the hydrogels were in the range 34.6-37.5°C, close to the body temperature, and the amount of hydrophilic moieties in the polymeric network allows to collect shrinking/swelling transition temperatures higher than the LCST of NIPAAm homopolymers. In order to test the preformed materials as drug carriers, diclofenac diethylammonium salt (DDA) was chosen and drug entrapment percent was determined. Drug release profiles, in media at different temperature and pH, depend on hydrogels crosslinking degree and drug-bead interactions. By using semi-empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

series of novel cellulose membranes with antioxidant activity was prepared and characterized. Microcrystalline cellulose was functionalized with lipoic acid, ferulic acid and alpha-tocopherol moieties. These materials were characterized by FT-IR and NMR spectroscopy and their degree of substitution (DS) was determined by volumetric analysis. The manuscript discusses the antioxidant activity of cellulose derivatives in inhibiting lipid peroxidation in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals: 2,2′-azobis-(2-amidinopropane) (AAPH), which exogenously produces peroxyl radicals by thermal decomposition, and tert-butyl hydroperoxide (tert-BOOH), which endogenously produces alkoxyl radicals by Fenton reactions. Membranes were prepared by the nonsolvent-induced phase inversion technique. Membranes of the pure cellulose derivatives were thin, mechanically weak and generally unsuitable for practical application. As an alternative, mechanically resistant poly(vinylidene fluoride)/cellulose ester blend membranes were obtained by direct phase inversion of the polymer/polymer/solvent mixture. These membranes were characterized by means of water permeability measurements, optical and scanning electron microscopy, determination of the antioxidant activity in comparison with starting materials. The membranes exhibited a good preservation of peroxidation inhibition and the performance of this kind of cellulose membrane as a scavenger of Reactive Oxygen Species (ROS) offers interesting perspectives for an effective control of intradialytic oxidative stress. [ABSTRACT FROM AUTHOR]

Objectives To prove the possibility of covalently functionalizing multi-walled carbon nanotubes (CNTs) by free radical grafting of gallic acid on their surface with the subsequent synthesis of materials with improved biological properties evaluated by specific in-vitro assays. Methods Antioxidant CNTs were synthesized by radical grafting of gallic acid onto pristine CNTs. The synthesis of carbon nanotubes was carried out in a fixed-bed reactor and, after the removal of the amorphous carbon, the grafting process was performed. The obtained materials were characterized by fluorescence and Fourier transform infrared spectroscopy (FT-IR) analyses. After assessment of the biocompatibility and determination of the disposable phenolic group content, the antioxidant properties were evaluated in terms of total antioxidant activity and scavenger ability against 2,2′-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl and peroxyl radicals. Finally the inhibition activity on acetylcholinesterase was evaluated. Key findings The covalent fuctionalization of CNTs with gallic acid was confirmed and the amount of gallic acid bound per g of CNTs was found to be 2.1 ± 0.2 mg. Good antioxidant and scavenging properties were recorded in the functionalized CNTs, which were found to be able to inhibit the acetylcholinesterase with potential improved activity for biomedical and pharmaceutical applications. Conclusions For the first time, a free radical grafting procedure was proposed as a synthetic approach for the covalent functionalization of CNTs with an antioxidant polyphenol. [ABSTRACT FROM AUTHOR]

A novel, simple synthetic strategy for the preparation of crosslinked polymers with significant antioxidant properties is proposed. Ferulic acid (FA), a well‐known antioxidant compound, due to its reactivity toward free radical process, was inserted into a polymeric network with methacrylic acid (MAA) and ethylene glycole dimethacrylate acting as comonomer and crosslinker, respectively. All the reactants were simultaneously mixed in the polymerization feed and one‐pot radical reaction was carried out. Irregular microparticles were prepared by bulk polymerization and microspheres by precipitation polymerization. The materials were characterized by nuclear magnetic resonance–magic angle spinning (NMR‐MAS) studies, to verify effective FA insertion into polymeric networks, and by morphological, dimensional analyses, and water absorption measurement to study their superficial and swelling properties, respectively. Antioxidant properties of materials were evaluated by linoleic acid emulsion system–thiocyanate assay, determination of scavenging activity on DPPH radicals, determination of available phenolic groups in polymeric matrices, and determination of total antioxidant capacity. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this work, the possibility to employ molecularly imprinted polymers as base excipients for controlled drug delivery devices was demonstrated. As template molecule, our attention was focused on phytic acid, a water soluble antioxidant compound. The possibility to raise a controlled/sustained release of an antioxidant agent is very useful from an application point of view; in recent years, indeed, biomedical applications of antioxidants have greatly grown because the link between human diseases and oxidative stress were proved. Polymers were synthesized using methacrylic acid as functional monomer and N,N′-Ethylenebis(acrylamide) as crosslinker. After the evaluation of the imprinting efficiency of the synthesized materials by binding experiments in which the percentage of phytic acid bounded by the molecularly imprinted polymers was found to be remarkably higher compared to the non-imprinted ones, MIP were tested as a controlled release device for the antioxidant in gastrointestinal simulating fluids. [ABSTRACT FROM AUTHOR]

In this study, we report the results of our investigations on the percutaneous permeation profiles of Diclofenac sodium, Paracetamol, Propanolol hydrochloride, and α-Tocopherol from the different lyotropic liquid crystalline phases obtained by Pluronic P105/water mixtures, in order to understand if the particular assembly shown in the formulations could influence the delivery across the skin. Recent studies have focused on the Pluronic liquid crystalline phases to evaluate the potential use of these phases in drug delivery, but no comparative investigation has been yet performed on the drug permeation from the different liquid crystalline phases obtained by the same Pluronic surfactant. The cubic, hexagonal, and lamellar mesophases (loading the above-mentioned drug) were characterized by Deuterium Nuclear Magnetic Resonance spectroscopy and Polarized Optical Microscopy observations. Results revealed that the liquid crystalline gel microscopic structure obtained in the different formulations drastically affects the drug percutaneous availability. As a consequence these systems could be proposed as novel transdermal drug delivery systems. [ABSTRACT FROM AUTHOR]

This paper deals with the synthesis of thermo-responsive microspheres with proteic structure exhibiting a transition temperature close to the body temperature. Temperature-sensitive hydrogels have attracted extensive interest due to their potential and promising applications in drug delivery field since they can undergo a rapid and reversible phase transition from a swollen to a shrunken state depending on environmental temperature. The hydrogels were synthesized by free-radical polymerization of hydrolyzed methacrylated gelatin (HGel-MA) and N, N′-methylenebisacrylamide as pro-hydrophilic multifunctional macromer and crosslinker, respectively, and N-isopropylacrylamide as thermo-responsive monomer. Thermal analyses showed negative thermo-responsive behavior for all compositions and, by increasing the content of the hydrophilic moieties in the network, the transition temperature raised to 36.9°C, close to the physiological values. In order to test the materials as drug carriers, diclofenac sodium salt was chosen as model drug. Drug release profiles, in phosphate buffer solution (pH 7.0, 10−3 M) at 25 and 40°C, depend on the hydrogel’s crosslinking degree and hydrophilic/hydrophobic balance in the polymeric network. For all formulations, in the shrunken state, the drug release percent values ranged from 80% to 100% after 24 h, and after 3 h, more than 60% of therapeutics was delivered. On the contrary, the swelling of the loaded microparticles produces, even after 30 h, a drug release percent of about 75%. By using semi-empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. The physico-chemical characteristics of thermo-responsive materials confirm the applicability of the microspheres as drug delivery device. [ABSTRACT FROM AUTHOR]