Jasna Djonlagic

Synthesis and characterization of biodegradable poly(butylene succinate-co-butylene fumarate)s

Abstract A series of aliphatic biodegradable polyesters modified with fumaric residues was synthesized by transesterification in the melt of dimethyl succinate, dimethyl fumarate and 1,4-butanediol. The amount of unsaturation, originating from the fumaric acid residues in the polyesters chains was varied from 5 to 20 mol%. The molecular structure and composition of the polyesters were determined by 1H NMR spectroscopy. The effects of the content of fumaric residues on the thermal and thermo-oxidative properties of the synthesized polyesters were investigated using differential scanning calorimetry (DSC) and thermogravimetric analysis. The degree of crystallinity was determined by DSC and wide angle X-ray scattering. The degrees of crystallinity of the unsaturated copolyesters were reduced, while the melting temperatures were higher in comparison to poly(butylene succinate). Biodegradation of the synthesized copolyesters was estimated in enzymatic degradation tests using a buffer solution with Rhizopus arrhizus lipase at 37 °C. Although the degree of crystallinity of the copolyesters decreases slightly with increasing unsaturation, the biodegradation is not enhanced suggesting that not only the chemical structure and molecular stiffness but also the morphology of the spherulites has an influence on the biodegradation properties. The highest biodegradability was observed for the copolyesters containing 5 and 10 mol% of fumarate units.

Rheological study of the copolymerization reaction of acrylate‐terminated unsaturated copolyesters with styrene

The free radical copolymerization reaction of three series of acrylate-terminated unsaturated polyesters with styrene, using benzoyl peroxide/N,N -dimethylaniline as the redox initiator system, was followed by dynamic mechanical analysis. The presence of double bonds at both chain ends allows the formation of a regular network during the crosslinking copolymerization with styrene. The evolution of the rheological parameters, such as storage modulus G ′ and loss modulus G″, was recorded. The polymerization reaction, leading to the formation of a crosslinked structure, is described by a second order phenomenological equation, which takes into account a self-acceleration effect, as a consequence of not only the chemical reaction of crosslinking after the gel point but also phase segregation. This rheokinetic model of curing acrylate-terminated polyesters permits the determination of the numerical values of the kinetic equation constants and the degree of rheological conversion as a function of cure time. The influence of the terminal double bonds as well as of the cis-trans configuration on the curing kinetics of the unsaturated copolyesters was evaluated.

Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): Assessment of biocompatibility

Properties and biocompatibility of a series of thermoplastic poly(urethane-siloxane)s (TPUSs) based on α,ω-dihydroxy ethoxy propyl poly(dimethylsiloxane) (PDMS) for potential biomedical application were studied. Thin films of TPUSs with a different PDMS soft segment content were characterized by (1) H NMR, quantitative (13) C NMR, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), contact angle, and water absorption measurements. Different techniques (FTIR, AFM, and DMA) showed that decrease of PDMS content promotes microphase separation in TPUSs. Samples with a higher PDMS content have more hydrophobic surface and better waterproof performances, but lower degree of crystallinity. Biocompatibility of TPUSs was examined after attachment of endothelial cells to the untreated copolymer surface or surface pretreated with multicomponent protein mixture, and by using competitive protein adsorption assay. TPUSs did not exhibit any cytotoxicity toward endothelial cells, as measured by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assays. The untreated and proteins preadsorbed TPUS samples favored endothelial cells adhesion and growth, indicating good biocompatibility. All TPUSs adsorbed more albumin than fibrinogen in competitive protein adsorption experiment, which is feature regarded as beneficial for biocompatibility. The results indicate that TPUSs have good surface, thermo-mechanical, and biocompatible properties, which can be tailored for biomedical application requirements by adequate selection of the soft/hard segments ratio of the copolymers.

In Vitro Biocompatibility Evaluation of Novel Urethane–Siloxane Co-Polymers Based on Poly(ϵ-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(ϵ-Caprolactone)

Abstract Novel polyurethane co-polymers (TPUs), based on poly(ϵ-caprolactone)-block-poly(dimethylsiloxane)-block-poly(ϵ-caprolactone) (PCL-PDMS-PCL) as soft segment and 4,4’-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as hard segment, were synthesized and evaluated for biomedical applications. The content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%. The influence of the content and length of the HS on the thermal, surface, mechanical properties and biocompatibility was investigated. The structure, composition and HS length were examined using 1H- and quantitative 13C-NMR spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments participated. It was found that an increase in the average HS length (from 1.2 to 14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the hard segments, storage moduli, hydrophilicity and degree of microphase separation of the co-polymers. Depending on the HS content, a gradual variation in surface properties of co-polymers was revealed by FT-IR, AFM and static water contact angle measurements. The in vitro biocompatibility of co-polymers was evaluated using the endothelial EA.hy926 cell line and protein adsorption on the polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen from multicomponent protein mixture, which may indicate biocompatibility. The polyurethane films with high HS content and/or high roughness coefficient exhibit good surface properties and biocompatible behavior, which was confirmed by non-toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic chemistry of the co-polymers makes them good candidates for further development as biomedical implants.

Synthesis and rheological study of some maleic acid and fumaric acid stereoregular polyesters, 10. Synthesis and characterization of α,ω-dihydroxyoligo(alkylene maleate)s†

α,ω-Dihydroxyoligojalkylene maleate)s with molecular weights ranging from 1500 to 4000 were prepared by polycondensation, in l-methyl-2-pyrrolidone at 105°C, of potassium maleate and 1,4-dibromobutane, 1,6-dibromohexane or 1,8-dibromooctane in the presence of 2-bromoethanol. The structure of oligomers was checked by 1 H and 13 C NMR spectroscopy. In most cases the mean functionality of oligomers is reasonably close to two.

Release behaviour of carbamazepine-loaded poly(ε-caprolactone)/poly(ethylene oxide) microspheres

Poly(ε-caprolactone) (PCL), a biodegradable and biocompatible aliphatic polyester has a great potential as a drug carrying material in controlled drug delivery/release systems. The most simple and economical way to tailor the release profile of active substances from biodegradable polymer matrix is by the addition of the second polymeric component in the polymer matrix, i.e. by blending. This study describes the preparation and characterization of a carbamazepine-loaded microspheres by the use of PCL blended with poly(ethylene oxide) as a drug carrying material. By the use of two-component hydrophilic/hydrophobic polymer blend as a microspheres’ matrix material, release profile of the drug can be modified and dictated. The microspheres prepared by classical oil-in-water emulsion solvent evaporation technique were characterized with respect to particle size and morphology, polymer matrix composition, encapsulation efficiency, physical state of the drug and in vitro release behaviour. It was presented that the release profile can be modified by the presence and the amount of hydrophilic component in the starting formulation of microspheres.

Poly(urethane‐dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells

Polyurethane copolymers based on α,ω-dihydroxypropyl poly(dimethylsiloxane) (PDMS) with a range of soft segment contents were prepared by two-stage polymerization, and their microstructures, thermal, thermomechanical, and surface properties, as well as in vitro hemo- and cytocompatibility were evaluated. All utilized characterization methods confirmed the existence of moderately microphase separated structures with the appearance of some microphase mixing between segments as the PDMS (i.e., soft segment) content increased. Copolymers showed higher crystallinity, storage moduli, surface roughness, and surface free energy, but less hydrophobicity with decreasing PDMS content. Biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact, an extraction method and after pretreatment of copolymers with multicomponent protein mixture, as well as by a competitive protein adsorption assay. Copolymers showed no toxic effect to endothelial cells and all copolymers, except that with the lowest PDMS content, exhibited resistance to endothelial cell adhesion, suggesting their unsuitability for long-term biomedical devices which particularly require re-endothelialization. All copolymers exhibited excellent resistance to fibrinogen adsorption and adsorbed more albumin than fibrinogen in the competitive adsorption assay, suggesting their good hemocompatibility. The noncytotoxic chemistry of these synthesized materials, combined with their nonadherent properties which are inhospitable to cell attachment and growth, underlie the need for further investigations to clarify their potential for use in short-term biomedical devices.

Influence of the chemical structure of poly(urea-urethane-siloxane)s on their morphological, surface and thermal properties

Segmented poly(urethane-urea-siloxane)s (PUUS) were synthesized using 4,4′-methylenediphenyl diisocyanate (MDI) and ethylene diamine (ED) as the hard segment components and hydroxypropyl-terminated poly(dimethylsiloxane) (PDMS) as the soft segment component, where the hard segment content ranged from 38 to 65 wt%. Segmented PUUSs were prepared by a two-step polymerization procedure in tetrahydrofuran/N-methylpyrrolidone (THF/NMP) mixture with a large proportion of polar solvent. The structure, composition and hard segment length were determined by 13C NMR and two-dimensional correlation spectroscopy. Thermal, mechanical, small-angle X-ray scattering and hydrogen bonding analyses indicated the formation of the microphase-separated copolymers with high tensile strength. Globular superstructures observed in the copolymer films by scanning electron microscopy (SEM) and atomic force microscopy (AFM) were probably arisen from the microstructural organization of the MDI-ED segments, depending on their content and length. The PUUS copolymers showed high water resistance and became more hydrophobic with increasing weight fraction of PDMS.

Synergistic anti-biofouling effect of Ag-exchanged zeolite and D-Tyrosine on PVC composite against the clinical isolate of Acinetobacter baumannii.

Due to their susceptibility to bacterial biofilm formation, commercial tubes for medical use are one of the main sources of hospital infections with Acinetobacter baumannii. The anti-biofouling activity of novel composites against the clinical isolate of the multi-drug resistant A. baumannii is reported here. The composites were prepared by addition of micronised silver-exchanged natural zeolite (Ag-NZ) into poly(vinyl chloride) (PVC), followed by coating of the composites with D-Tyrosine (D-Tyr). The Ag-NZ composites (containing 1–15 wt% of Ag-NZ) coated with D-Tyr (Ag-NZ-Tyr) showed a bactericidal effect (100% or a 6.9 log CFU reduction) towards immobilised bacterial cells. The uncoated Ag-NZ composites showed a reduction of up to 70% (4.4 log CFU) of immobilised bacteria in comparison with the original PVC. Rheological testing of the composites revealed that the addition of Ag-NZ slightly affected processability and formability of the PVC and increased the elasticity of the polymer matrix.

Influence of a low content of PEO segment on the thermal, surface and morphological properties of triblock and diblock PCL copolymers

Two series, one of triblock (PCL/PEO/PCL) and the other of diblock (PCL/PEO) copolymers were prepared by ring-opening polymerization of ε-caprolactone catalized with tin(II) octoate and by using dihydroxy or monohydroxy poly(ethylene oxide) as the macroinitiator. The PEO block length was fixed (Mn 1,000 g/mol) and the PCL block lengths (Mn 10,000-40,000 g/mol) were tailored by changing weight ratio of ε-CL/PEO. The copolymers’ structure was confirmed by 1H and quantitative 13C NMR spectroscopy while their molecular weights were determined by GPC analysis. The thermal properties and the degree of crystallinity of the copolymers were investigated and compared by using DSC and WAXS. Both types of copolymers were semicrystalline with the orthorhombic PCL crystal lattice. The surface morphology of the copolymer films was investigated by using optical microscopy and AFM analysis, which confirmed the spherulitic lamellar structure with spherulites of different diameters. Data indicated that a low content of PEO segment had an influence on thermal degradation behavior, crystallinity and morphology of copolymers. Roughness of copolymer films was affected by the content of PEO and correlated with the spherulites’ diameter. The small changes in water and moisture absorption properties of copolymers compared to homopolymer PCL were observed.