Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol.

Scaffolds constituted by electrospun microfibers of poly(ethylene glycol) (PEG) and poly(butylene succinate) (PBS) were studied. Specifically, coaxial microfibers having different core-shell distributions and compositions were considered as well as uniaxial micro/nanofibers prepared from mixtures of both polymers. Processing conditions were optimized for all geometries and compositions and resulting morphologies (i.e. diameter and surface texture) characterized by scanning electron microscopy. Chemical composition, molecular interactions and thermal properties were evaluated by FTIR, NMR, XPS and differential scanning calorimetry. The PEG component of electrospun fibers could be solubilized by immersion of scaffolds in aqueous medium, giving rise to high porosity and hydrophobic samples. Nevertheless, a small amount of PEG was retained in the PBS matrix, suggesting some degree of mixing. Solubilization was slightly dependent on fiber structure; specifically, the distribution of PEG in the core or shell of coaxial fibers led to higher or lower retention levels, respectively. Scaffolds could be effectively loaded with hydrophobic drugs having antibacterial and anticarcinogenic activities like triclosan and curcumin, respectively. Their release was highly dependent on their chemical structure and medium composition. Thus, low and high release rates were observed in phosphate buffer saline (SS) and SS/ethanol (30:70 v/v), respectively. Slight differences in the release of triclosan were found depending on fiber distribution and composition. Antibacterial activity and biocompatibility were evaluated for both loaded and unloaded scaffolds.

Anhydric maleic functionalization and polyethylene glycol grafting of lactide-co-trimethylene carbonate copolymers.

Lactide and trimethylene carbonate copolymers were successfully grafted with polyethylene glycol via previous functionalization with maleic anhydride and using N,N'-diisopropylcarbodiimide as condensing agent. Maleinization led to moderate polymer degradation. Specifically, the weight average molecular weight decreased from 36,200 to 30,200 g/mol for the copolymer having 20 mol% of trimethylene carbonate units. Copolymers were characterized by differential scanning calorimetry, thermogravimetry and X-ray diffraction. Morphology of spherulites and lamellar crystals was evaluated with optical and atomic force microscopies, respectively. The studied copolymers were able to crystallize despite the randomness caused by the trimethylene carbonate units and the lateral groups. Contact angle measurements indicated that PEG grafted copolymers were more hydrophilic than parent copolymers. This feature justified that enzymatic degradation in lipase medium and proliferation of both epithelial-like and fibroblast-like cells were enhanced. Grafted copolymers were appropriate to prepare regular drug loaded microspheres by the oil-in-water emulsion method. Triclosan release from loaded microspheres was evaluated in two media.

Restricted puckering of mineralized RNA-like riboses.

The pseudorotational motions of highly hydroxylated pentafuranose sugars in the free state and tethered to hydroxyapatite have been compared. The conformation pentafuranose ring remains restricted at the North region of the pseudorotational wheel, which is the one typically observed for nucleosides and nucleotides in the double helix A-RNA, when the phosphate-bearing sugar is anchored to the mineral surface. Results indicate that the severe restrictions imposed by the mineral are responsible of the double helix preservation when DNA and RNA are encapsulated in crystalline nanorods.

Sensitive thermal transitions of nanoscale polymer samples using the bimetallic effect: application to ultra-thin polythiophene.

A sensitive nanocalorimetric technology based on microcantilever sensors is presented. The technology, which combines very short response times with very small sample consumption, uses the bimetallic effect to detect thermal transitions. Specifically, abrupt variations in the Young's modulus and the thermal expansion coefficient produced by temperature changes have been employed to detect thermodynamic transitions. The technology has been used to determine the glass transition of poly(3-thiophene methyl acetate), a soluble semiconducting polymer with different nanotechnological applications. The glass transition temperature determined using microcantilevers coated with ultra-thin films of mass = 10(-13) g is 5.2 °C higher than that obtained using a conventional differential scanning calorimeter for bulk powder samples of mass = 5 × 10(-3) g. Atomistic molecular dynamics simulations on models that represent the bulk powder and the ultra-thin films have been carried out to provide understanding and rationalization of this feature. Simulations indicate that the film-air interface plays a crucial role in films with very small thickness, affecting both the organization of the molecular chains and the response of the molecules against the temperature.

LACDIF, a new electron diffraction technique obtained with the LACBED configuration and a C(s) corrector: comparison with electron precession.

By combining the large-angle convergent-beam electron diffraction (LACBED) configuration together with a microscope equipped with a C(s) corrector it is possible to obtain good quality spot patterns in image mode and not in diffraction mode as it is usually the case. These patterns have two main advantages with respect to the conventional selected-area electron diffraction (SAED) or microdiffraction patterns. They display a much larger number of reflections and the diffracted intensity is the integrated intensity. These patterns have strong similarities with the electron precession patterns and they can be used for various applications like the identification of the possible space groups of a crystal from observations of the Laue zones or the ab-initio structure identifications. Since this is a defocused method, another important application concerns the analysis of electron beam-sensitive materials. Successful applications to polymers are given in the present paper to prove the validity of this method with regards to these materials.

Microspheres from new biodegradable poly(ester amide)s with different ratios of L- and D-alanine for controlled drug delivery.

A series of biodegradable poly (ester amide)s composed of sebacic acid, dodecanediol and different ratios of the stereoisomers of L- and D-alanine were synthesized for applications in drug delivery systems. Microspheres loaded with diclofenac sodium salt, triclosan and clofazimine were prepared with the solvent evaporation technique. No influence of polymer constitution in the drug release rate was found in vitro and no degradation occurred during the period of drug release. It was shown that a sustained delivery of the hydrophilic diclofenac sodium salt in Sörensen media occurred and it was controlled by diffusion. However, exhaustion of microspheres was feasible only from the most porous matrices where channelling had an important contribution.

Structural versatility of oxalamide-based compounds: a computational study on the isomerization of the oxalamide group and the structural preferences of the polyoxalamides.

The conformational properties of the oxalamide group and crystal structure of several polyoxalamides have been investigated by computational methods. First, a detailed quantum mechanical study of the conformational preferences of N,N'-dimethyloxalamide is reported. Results, which were obtained at the MP2/6-31G(d) level, provide not only the minimum energy conformations but also a description of the energetics and structural changes associated to the isomerization process of the oxalamide group. These quantum mechanical results together with those obtained from additional calculations have been used to develop a set of force-field parameters for the oxalamide group. Molecular mechanics calculations have been performed to test the parameters and to provide new information in terms of energy contributions about the isomerization of the oxalamide group. On the other hand, the new set of parameters has been used to investigate the structural preferences of polyoxalamides (-[NH-CO-CO-NH-(CH(2))(n)]-) by PCSP calculations. Results indicated that polyoxalamides with an even number of methylene groups adopt a structure with one hydrogen bonding direction, whereas polymers with an odd number of methylene groups prefer a structure with two hydrogen bonding directions. The latter crystal structure is completely different from that observed in conventional polyamides and has been investigated in detail through Monte Carlo simulations.

Dimethyl N,N'-oxalamidodiethanoate.

The title compound, dimethyl 2,2'-(oxalyldiimino)diethanoate, C(8)H(12)N(2)O(6), exhibits a network of hydrogen bonds between amide and ester groups. Molecules lie on inversion centres and show a planar conformation for both the oxalamide and ester groups. The glycine residues adopt a conformation close to the polyglycine II structure.

Towards the understanding of the folding of methylene units in the glutamine residue.

The conformational preferences of the methylenic sequence in the side chain of the glutamine residue were investigated by ab initio and semi-empirical quantum mechanical calculations and examination of both the Brookhaven Protein Databank and Cambridge Structural Data Base. The results were analysed on the basis of our previous findings about the folding of methylene groups in aliphatic segments. Both energy calculations and the crystallographic structure of small peptides indicate that methylene units of the glutamine residue tend to fold in a gauche conformation. In contrast, such groups usually adopt an all-trans conformation in proteins due basically to the entropic and solvent contributions. These results have been demonstrated by computing the entropic correction to the free energy and evaluating the solvent effects through SCRF calculations.

Incorporation of diacids into the polyglycine II structure: model studies.

Aliphatic diacids are often incorporated into polypeptide structures in order to obtain model compounds for hormones, protein turns, etc. They are also fundamental components of many commercial polyamides. On the other hand glycine, the simplest amino acid, shows unique conformational features. In order to better understand the structure of such compounds, we have synthetized and determined the molecular structure of three models represented by the general formula CH3-CH2-CH2-NH-CO-CH2-NH-CO-(CH2)n-2-CO-NH-CH2-CO-NH-CH2-CH2-CH3, with n = 3, 4, or 6. Conformational differences have been found in the dicarboxylic moiety, whereas glycine always has the polyglycine II conformation. The -CO-(CH2)n-2-CO-segment adopts a folded conformation: SS, TGT, and SGTGS for n = 3, 4, and 6, respectively. Molecular packing is always pseudohexagonal and a network of hydrogen bonds oriented in three directions at 120 degrees is formed. The results are of interest in order to provide information about polyamides in which glycine residues are incorporated. Our results confirm the tendency of glycine residues to adopt the polyglycine II conformation in its copolymers with aliphatic compounds.

Crystal structure of a helical oligopeptide model of polyglycine II and of other polyamides: acetyl-(glycyl-beta-alanyl)2-NH propyl.

We synthesized and solved the crystalline structure of the oligopeptide acetyl-(glycyl-beta-alanyl)2-NH propyl. The crystal is formed by layers of helical molecules with the same chirality; however, right-handed layers alternate with left-handed ones. Inside every layer, the packing of helices is pseudohexagonal with hydrogen bonds between neighbor molecules. The structure found affords direct support for the model proposed by Crick and Rich for polyglycine II and also provides an interpretation for the structure of a newly found family of polyamides that do not form sheets as observed in most nylon structures.

Crystals of polyglycine in the beta form.

Well-defined lamellar crystals of polyglycine I (the beta modification of polyglycine) have been grown from a solution of a sample of 5000 molecular weight. The crystals are elongated and have an average thickness of 40 to 50 A. The unit cell is monoclinic and the crystals have a twined structure. Electron diffraction reveals that the polypeptide chains are normal to the basal plane of the crystals and that the hydrogen bonds are parallel to their long sides. From these data we conclude that crystals of polyglycine I have a folded beta structure.