Photo-crosslinked chitosan-gelatin xerogel-like coating onto "cold" plasma functionalized poly(lactic acid) film as cell culture support.

This paper reports on biofunctionalisation of a poly(lactic acid) (PLA) film by surface activation through cold plasma treatment followed by coating with a chitosan-gelatin xerogel. The UV cross-linking of the xerogel precursor was simultaneously performed with the fixation onto the PLA support. This has a strong effect on surface properties, in terms of wettability, surface free energy, morphology and micromechanical features. The hydrophilic - hydrophobic character of the surface, determined by contact angle measurements, was tuned along the process, passing from moderate hydrophobic PLA to enhanced hydrophilic plasma activated surface, which favors coating adhesion, then to moderate hydrophobic chitosan-gelatin coating. The coating has a Lewis amphoteric surface, with a porous xerogel-like morphology, as revealed by scanning electron microscopy images. By riboflavin mediated UV cross-linking the chitosan-gelatin coating becomes high adhesive and with a more pronounced plasticity, as shown by AFM force-distance spectroscopy. Thus prepared surface-coated PLA supports were successfully tested for growth of dermal fibroblasts, which are known for their induction potential of chondrogenic cells, which is very important in cartilage tissue engineering.

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

One-Step Preparation of Carboxymethyl Cellulose-Phytic Acid Hydrogels with Potential for Biomedical Applications.

Hydrogels based on natural, biodegradable materials have gained considerable interest in the medical field due to their improved drug delivery profiles and tissue-mimicking architecture. In this regard, this study was devoted to the preparation and characterization of new physically crosslinked hydrogels based on carboxymethyl cellulose and an unconventional crosslinking agent, phytic acid. Phytic acid, in addition to its antioxidant and antibacterial effects, can improve the biological properties and stability of gels, without adding toxicity. Fourier transform infrared (FTIR) spectroscopy, rheological studies and thermal analysis confirmed the hydrogel formation. The influence of the ratio between the cellulose derivative and the crosslinker upon the morphological structure and water uptake was evidenced by scanning electron microscopy (SEM) and swelling measurements in simulated body fluids. Furthermore, procaine was entrapped within the hydrogels and used as a model drug for in vitro studies, which highlighted the dependence of the drug release on the phytic acid content of the matrix. The materials demonstrated antibacterial effects against Escherichia coli and Staphylococcus aureus bacteria. The biocompatibility was assessed on fibroblast cells, and according to our results, hydrogels can improve cell viability highlighting the potential of these systems as therapeutic scaffolds for skin tissue engineering.

MWCNTs Composites-Based on New Chemically Modified Polysulfone Matrix for Biomedical Applications.

Polyvinyl alcohol (PVA) is a non-toxic biosynthetic polymer. Due to the hydrophilic properties of the PVA, its utilization is an easy tool to modify the properties of materials inducing increased hydrophilicity, which can be noticed in the surface properties of the materials, such as wettability. Based on this motivation, we proposed to obtain high-performance composite materials by a facile synthetic method that involves the cross-linking process of polyvinyl alcohol (PVA) with and aldehyde-functionalized polysulfone(mPSF) precursor, prior to incorporation of modified MWCNTs with hydrophilic groups, thus ensuring a high compatibility between the polymeric and the filler components. Materials prepared in this way have been compared with those based on polyvinyl alcohol and same fillers (mMWCNTs) in order to establish the influence of the polymeric matrix on the composites properties. The amount of mMWCNTs varied in both polymeric matrices between 0.5 and 5 wt%. Fourier transformed infrared with attenuated total reflectance spectroscopy (FTIR-ATR) was employed to confirm the changes noted in the PVA, mPSF and their composites. Hemolysis degree was investigated in correlation with the material structural features. Homogenous distribution of mMWCNTs in all the composite materials has been confirmed by scanning electron microscopy. The hydrophilicity of both composite systems, estimated by the contact angle method, was influenced by the presence of the filler amount mMWCNTs in both matrices (PVA and mPSF). Our work demonstrates that mPSF/mMWCNTs and PVA/mMWCNTs composite could be used as water purification or blood-filtration materials.

Effect of Gamma Irradiation on the PLA-Based Blends and Biocomposites Containing Rosemary Ethanolic Extract and Chitosan.

The irradiation of polymeric materials with ionizing radiation (γ-rays, X-rays, accelerated electrons, ion beams, etc.) may lead to disproportion, hydrogen abstraction, arrangements, degradation, and/or the formation of new bonds. The purpose of this paper is to evaluate the effect of gamma irradiation on some new poly(lactic acid) (PLA)-based blends and biocomposites, which is crucial when they are used for food packaging or medical purposes. The polymeric blends and biocomposites based on PLA and rosemary ethanolic extract (R) and poly(ethylene glycol) (PEG) (20 wt%) plasticized PLA, chitosan (CS) (3-6 wt%) and R (0.5 wt%) biocomposites were subjected to gamma irradiation treatment using three low γ-doses of 10, 20, and 30 kGy. The effect of irradiation was evaluated by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), thermogravimetry (TG), chemiluminescence method (CL), migration studies, and antibacterial activity tests. It was found that in comparison with neat PLA, the gamma irradiation in the oxidative conditions of the PLA-based blends and biocomposites, causes modifications in the structure, morphology, and thermal properties of the materials depending on irradiation dose and the presence of natural additives such as rosemary and chitosan. It was established that under a gamma-irradiation treatment with dose of 10-20 kGy, the PLA materials showed minor changes in structure and properties being suitable for application in packaging and in addition after irradiation with such doses their antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium is improved.

New Hydrogel Network Based on Alginate and a Spiroacetal Copolymer.

This study reports a strategy for developing a biohybrid complex based on a natural/synthetic polymer conjugate as a gel-type structure. Coupling synthetic polymers with natural compounds represents an important approach to generating gels with superior properties and with potential for biomedical applications. The study presents the preparation of hybrid gels with tunable characteristics by using a spiroacetal polymer and alginate as co-partners in different ratios. The new network formation was tested, and the structure was confirmed by FTIR and SEM techniques. The physical properties of the new gels, namely their thermal stability and swelling behavior, were investigated. The study showed that the increase in alginate content caused a smooth increase in thermal stability due to the additional crosslinking bridges that appeared. Moreover, increasing the content of the synthetic polymer in the structure of the gel network ensures a slower release of carvacrol, the encapsulated bioactive compound.

Alginate enriched with phytic acid for hydrogels preparation. Therapeutic applications.

In the last decade, numerous innovative strategies have been used to obtain highly efficient synthetic or semi-synthetic biomaterials. Between these innovative biomaterials, hydrogels occupy a distinct place due to their superior biological and physico-chemical characteristics. Alginate is a natural linear polysaccharide with important physico-chemical and biological properties. Recently, we obtained a new hydrogel based on alginate and phytic acid with improved physico-chemical properties. In the present study, the hydrogels previously obtained were tested in terms of their biological properties and possibilities of use in the biomedical field. For this purpose, the hydrogels were loaded with norfloxacin (NRF), an antibacterial compound utilised in the treatment against Gram-negative and Gram-positive organisms. Unfortunately, NRF has low solubility and permeability. In order to provide protection against loss, but also for enhanced bioavailability, and controlled-release of norfloxacin, a drug inclusion complex with cyclodextrin was realized. The effect of complexation on the release profile was highlighted. The addition of NRF to the hydrogel matrices greatly improved the antibacterial activity of the tested compounds. The presence of CD did not affect the homogeneity of the drug distribution. Changes in the polymeric matrix structure were registered after the incorporation of the drug, which were attributed to the relaxation of the network subsequently to the penetration and diffusion of the drug solution simultaneously with the swelling process. The release of NRF from Alg_PA polymeric network has been successfully modulated by the use of CD as a host molecule.

New cellulose-collagen-alginate materials incorporated with quercetin, anthocyanins and lipoic acid.

Herein we present a new biomaterial based on cellulose, collagen and sodium alginate which served as a matrix for the incorporation of bioactive substances with antioxidant properties. Compared with pure cellulose hydrogels, the compressive strength and the elastic modulus of cellulose-collagen-alginate hydrogels were significantly enhanced, thus the compressive strength increased from 0.256 kPa to 6.91 kPa, while the elastic modulus increased from 0.0023 kPa to 0.115 kPa at 30% strain level. The release kinetic of all drugs through matrix components was done according to the Korsmeyer-Peppas model with a Fickian diffusion. The presence of bioactive principles, quercetin, lipoic acid and anthocyanins, gives biomaterials an antioxidant capacity on average 30% higher compared to the base matrix. The mechanical resistance, mucoadhesiveness, bioadhesiveness, release kinetic, and antioxidant capacity of active principles, recommend these biomaterials for the manufacture of transdermal drug delivery devices.

Radiation Processing and Characterization of Some Ethylene-propylene-diene Terpolymer/Butyl (Halobutyl) Rubber/Nanosilica Composites.

Composites based on ethylene-propylene-diene terpolymer (EPDM), butyl/halobutyl rubber and nanosilica were prepared by melt mixing and subjected to different doses of electron beam irradiation. The effect of irradiation dose on the mechanical properties, morphology, glass transition temperature, thermal stability and water uptake was investigated. The efficiency of the crosslinking by electron beam irradiation was analyzed by Charlesby-Pinner parameter evaluation and crosslink density measurements. The scanning electron microscopy data showed a good dispersion of nanosilica in the rubber matrix. An improvement in hardness and 100% modulus was revealed by increasing irradiation dose up to 150 kGy. The interaction between polymer matrix and nanosilica was analyzed using the Kraus equation. Additionally, these results indicated that the mechanical properties, surface characteristics, and water uptake were dependent on crosslink characteristics.

Development and Performance of Bioactive Compounds-Loaded Cellulose/Collagen/Polyurethane Materials.

Here we present a new biomaterial based on cellulose, collagen and polyurethane, obtained by dissolving in butyl imidazole chloride. This material served as a matrix for the incorporation of tannin and lipoic acid, as well as bioactive substances with antioxidant properties. The introduction of these bioactive principles into the base matrix led to an increase of the compressive strength in the range 105-139 kPa. An increase of 29.85% of the mucoadhesiveness of the film containing tannin, as compared to the reference, prolongs the bioavailability of the active substance; a fact also demonstrated by the controlled release studies. The presence of bioactive principles, as well as tannins and lipoic acid, gives biomaterials an antioxidant capacity on average 40%-50% higher compared to the base matrix. The results of the tests of the mechanical resistance, mucoadhesiveness, bioadhesiveness, water absorption and antioxidant capacity of active principles recommend these biomaterials for the manufacture of cosmetic masks or patches.

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers.

New trends in biomedical applications of the hybrid polymeric hydrogels, obtained by combining natural polymers with synthetic ones, have been reviewed. Homopolysaccharides, heteropolysaccharides, as well as polypeptides, proteins and nucleic acids, are presented from the point of view of their ability to form hydrogels with synthetic polymers, the preparation procedures for polymeric organic hybrid hydrogels, general physico-chemical properties and main biomedical applications (i.e., tissue engineering, wound dressing, drug delivery, etc.).

Biocompatible Materials Based on Plasticized Poly(lactic acid), Chitosan and Rosemary Ethanolic Extract I. Effect of Chitosan on the Properties of Plasticized Poly(lactic acid) Materials.

The purpose of the present study is to develop new multifunctional environmentally friendly materials having applications both in medical and food packaging fields. New poly(lactic acid) (PLA)-based multifunctional materials containing additives derived from natural resources like chitosan (CS) and rosemary extract (R) were obtained by melt mixing. Each of the selected components has its own specific properties such as: PLA is a biodegradable thermoplastic aliphatic polyester derived from renewable biomass, heat-resistant, with mechanical properties close to those of polystyrene and polyethylene terephthalate, and CS offers good antimicrobial activity and biological functions, while R significantly improves antioxidative action necessary in all applications. A synergy of their combination, an optimum choice of their ratio, and processing parameters led to high performance antimicrobial/antioxidant/biocompatible/environmentally degradable materials. The polyethylene glycol (PEG)-plasticized PLA/chitosan/powdered rosemary extract biocomposites of various compositions were characterized in respect to their mechanical and rheological properties, structure by spectroscopy, antioxidant and antimicrobial activities, and in vitro and in vivo biocompatibility. Scanning electron microscopy images evidence the morphology features added by rosemary powder presence in polymeric materials. Incorporation of additives improved elongation at break, antibacterial and antioxidant activity and also biocompatibility. Migration of bioactive components into D1 simulant is slower for PEG-plasticized PLA containing 6 wt % chitosan and 0.5 wt % rosemary extract (PLA/PEG/6CS/0.5 R) biocomposite and it occurred by a diffusion-controlled mechanism. The biocomposites show high hydrophilicity and good in vitro and in vivo biocompatibility. No hematological, biochemical and immunological modifications are induced by subcutaneous implantation of biocomposites. All characteristics of the PEG-plasticized PLA-based biocomposites recommend them as valuable materials for biomedical implants, and as well as for the design of innovative drug delivery systems. Also, the developed biocomposites could be a potential nature-derived active packaging with controlled release of antimicrobial/antioxidant compounds.

Interpenetrated polymer network with modified chitosan in composition and self-healing properties.

Smart hydrogels endowed with self-healing performance, enhanced stability and unique environmental responsiveness were prepared by interpenetrating the crosslinked poly(2-dimethylaminoethyl methacrylate) between the chains of the water-soluble maleoyl-chitosan. The influence of the ratio between the modified polysaccharide and the homopolymer upon the morphological structure and water uptake behaviour of the hydrogels was put in evidence by Scanning electron microscopy and swelling measurements in simulated body fluids. In addition, the synthesised compounds exhibited responsive properties, self-healing behaviour, and great availability like drug delivery systems. The in vitro study evidenced the dependence of the released procaine on the MAC content in the hydrogels, the release mechanism being controlled mainly by Fickian diffusion. The cytotoxicity assay on fibroblast demonstrated improved viability of cells by increasing the modified polysaccharide ratio into hydrogels. The self-repair capacity along with dual pH/thermo-responsiveness and biocompatibility of the hydrogels demonstrate their viability for various bio-applications.

Evaluation of the Rosemary Extract Effect on the Properties of Polylactic Acid-Based Materials.

New multifunctional materials containing additives derived from natural resources as powdered rosemary ethanolic extract were obtained by melt mixing and processed in good conditions without degradation and loss of additives. Incorporation of powdered rosemary ethanolic extract (R) into poly(lactic acid) (PLA) improved elongation at break, rheological properties, antibacterial and antioxidant activities, in addition to the biocompatibility. The good accordance between results of the chemiluminescence method and radical scavenging activity determination by chemical method evidenced the increased thermoxidative stability of the PLA biocomposites with respect to neat PLA, with R acting as an antioxidant. PLA/R biocomposites also showed low permeability to gases and migration rates of the bioactive compounds and could be considered as high-performance materials for food packaging. In vitro biocompatibility based on the determination of surface properties demonstrated a good hydrophilicity, better spreading and division of fibroblasts, and increased platelet cohesion. The implantation of PLA/R pellets, was proven to possess a good in vivo biocompatibility, and resulted in similar changes in blood parameters and biochemical responses with the control group, suggesting that these PLA-based materials demonstrate very desirable properties as potential biomaterials, useful in human medicine for tissue engineering, wound management, orthopedic devices, scaffolds, drug delivery systems, etc. Therefore, PLA/R-based materials show promising properties for applications both in food packaging and as bioactive biomaterials.

Effects of Electron Beam Irradiation on the Mechanical, Thermal, and Surface Properties of Some EPDM/Butyl Rubber Composites.

The effects of electron beam irradiation on the properties of ethylene propylene diene monomer (EPDM)/butyl rubber composites in presence of a polyfunctional monomer were investigated by means of differential scanning calorimetry (DSC), thermal analysis, scanning electron microscopy (SEM), attenuated total reflection absorption infrared spectroscopy (ATR-IR), and mechanical and surface energy measurements. The samples were exposed over a wide range of irradiation doses (20⁻150 kGy). The EPDM matrix was modified with butyl rubber, chlorobutyl rubber, and bromobutyl rubber. The gel content and crosslink density were found to increase with the electron beam irradiation dose. The values of the hardness and modulus increased gradually with the irradiation dose, while the tensile strength and elongation at break decreased with increasing irradiation dose. The EPDM/butyl rubber composites presented a higher thermal stability compared to the initial EPDM sample. The incorporation of butyl rubbers into the EPDM matrix led to an increase in material hydrophobicity. A similar trend was observed when the irradiation dose increased. The greatest change in the surface free energy and the contact angles occurs at an irradiation dose of 20 kGy. The Charlesby⁻Pinner plots prove the tendency to crosslinking as the irradiation dose increases.

Comparative Analysis of the Composition and Active Property Evaluation of Certain Essential Oils to Assess their Potential Applications in Active Food Packaging.

The antifungal, antibacterial, and antioxidant activity of four commercial essential oils (EOs) (thyme, clove, rosemary, and tea tree) from Romanian production were studied in order to assess them as bioactive compounds for active food packaging applications. The chemical composition of the oils was determined with the Folin-Ciocâlteu method and gas chromatography coupled with mass spectrometry and flame ionization detectors, and it was found that they respect the AFNOR/ISO standard limits. The EOs were tested against three food spoilage fungi-Fusarium graminearum, Penicillium corylophilum, and Aspergillus brasiliensis-and three potential pathogenic food bacteria-Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes-using the disc diffusion method. It was found that the EOs of thyme, clove, and tea tree can be used as antimicrobial agents against the tested fungi and bacteria, thyme having the highest inhibitory effect. Concerning antioxidant activity determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) methods, it has been established that the clove oil exhibits the highest activity because of its high phenolic content. Promising results were obtained by their incorporation into chitosan emulsions and films, which show potential for food packaging. Therefore, these essential oils could be suitable alternatives to chemical additives, satisfying the consumer demand for naturally preserved food products ensuring its safety.

Hybrid gels by conjugation of hyaluronic acid with poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)undecane) copolymers.

The approach of covalent conjugation for coupling synthetic polymers with biomolecules represents an appealing strategy to produce new compounds with distinctive properties for biomedical applications. In the present study we generated hybrid gels with tunable characteristics by using hyaluronic acid (HA) and four variants of poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5] undecane) (PITAU) copolymers, differing through the molar ratios between comonomers. The new bioconjugate compounds were realized by using a ″grafting to″ strategy, for further ensuring new ways for coupling of various bioactive compounds, taking into account that the grafted copolymers are dual sensitive to pH and temperature. The procedure of chemical crosslinking, by opening the anhydride cycle of the copolymer with the hydroxyl groups of hyaluronic acid, was used to prepare the bioconjugates. The chemical conjugation between HA and PITAU copolymers, as well as the structure of the new compounds, was confirmed by FTIR and NMR techniques. The physical properties of the new gels as thermal stability, swelling capacity, and rheological properties were investigated. The bioconjugate networks were also investigated as drug delivery carriers by using indomethacin as a model drug. In vitro and in vivo tests attested the homogeneity of the bioactive compounds as well as a good biochemical response, showing good biocompatibility for the new structures.

Toxicity, Biocompatibility, pH-Responsiveness and Methotrexate Release from PVA/Hyaluronic Acid Cryogels for Psoriasis Therapy.

Poly(vinyl alcohol)/hyaluronic acid cryogels loaded with methotrexate were studied. The physical⁻chemical characterization of cryogels was performed by FT-IR spectroscopy, scanning electron microscopy, differential scanning calorimetry and dynamic mechanical thermal analysis. Acute toxicity and haematological parameters were determined by "in vivo" tests. The biocompatibility tests proved that the obtained cryogels showed significantly decreased toxicity and are biocompatible. The pH-responsiveness of the swelling behaviour and of the methotrexate release from the poly(vinyl alcohol)/hyaluronic acid (PVA/HA) cryogels were studied in a pH interval of 2⁻7.4. A significant change in properties was found at pH 5.5 specific for treatment of affected skin in psoriasis disease.

IN VITRO TESTING OF XANTHAN/LIGNIN HYDROGELS AS CARRIERS FOR CONTROLLED DELIVERY OF BISOPROLOL FUMARATE.

AIM: To develop sustained release matrix tablets based on xanthan as highly water-soluble, cost-effective, non-toxic, easily available, and suitable hydrophilic systems. MATERIAL AND METHODS: Xanthan and lignin epoxy-modified resin (LER) mixture were crosslinked using epichlorohydrin as crosslinking agent leading to superabsorbent hydrogels with high swelling rate in aqueous mediums. RESULTS AND CONCLUSIONS: These hydrogels were tested as carries by the loading/delivery behaviour of bisoprolol fumarate in physiological conditions and based on the obtained results these hydrogels may show interest for application in medical and pharmaceutical areas. The amount of drug loaded in polymer networks was found to be ranging between 14.4% and 19.2%. Drug release was retarded and the release mechanism of the active principle was found to depend on matrix composition.