Carlos Elvira

Starch-based biodegradable hydrogels with potential biomedical applications as drug delivery systems.

The design and preparation of novel biodegradable hydrogels developed by the free radical polymerization of acrylamide and acrylic acid, and some formulations with bis-acrylamide, in the presence of a corn starch/ethylene-co-vinyl alcohol copolymer blend (SEVA-C), is reported. The redox system benzoyl peroxide (BPO) and 4-dimethylaminobenzyl alcohol (DMOH) initiated the polymerization at room temperature. Xerogels were characterized by 1H NMR and FTIR spectroscopies. Swelling studies were performed as a function of pH in different buffer solutions determining the water-transport mechanism that governs the swelling behaviour. Degradation studies of the hydrogels were performed in simulated physiological solutions for time up to 90 days, determining the respective weight loss, and analyzing the solution residue by 1H NMR. The mechanical properties of the xerogels were characterized by tensile and compressive tests, as well as by dynamo-mechanical analysis (DMA). Dynamo-mechanical parameters are also reported for hydrated samples.

Chemical modification of starch based biodegradable polymeric blends: effects on water uptake, degradation behaviour and mechanical properties

The main disadvantages of biodegradable polymers obtained from renewable sources are their dominant hydrophilic character, fast degradation rate and, in some cases, unsatisfactory mechanical properties particularly under wet environments. One possible solution to this problem is to reduce the water-uptake ability of these materials and to enhance the respective mechanical behaviour by chemical modification. In this work, three based starch blends with: (i) a copolymer of ethylene and vinyl alcohol (SEVA-C), (ii) cellulose acetate (SCA), and (iii) poly-e-caprolactone (SPCL); were chemically modified by chain crosslinking. This modification is based on the reaction between the starch hydroxyl groups and tri-sodium tri-meta phosphate. The obtained compounds were characterized by FTIR and the respective properties were assessed and compared to the original materials by means of the hydration degree, the degradation behaviour, contact angle measurements and mechanical testing. The results show that the water-uptake of these blends could be reduced up to 15% and that simultaneously stiffer materials with a less pronounced degradation rate can be obtained.

New partially degradable and bioactive acrylic bone cements based on starch blends and ceramic fillers

This work reports the development of new partially biodegradable acrylic bone cements based on corn starch/cellulose acetate blends (SCA), prepared by the free radical polymerization of methyl methacrylate and acrylic acid at low temperature. Amounts of biocompatible, osteoconductive and osteophilic mineral component such as hydroxylapatite (sintered and non-sintered), were incorporated in different percentages to confer a bone-bonding character to the bone cements in this type of applications. All cement formulations were characterized by 1H NMR spectroscopy. Curing parameters and mechanical properties were determined finding formulations which complete the ASTM legislation. Hydration degree, degradation studies, as well as bioactivity tests were performed in all prepared formulations. The developed systems show a range of properties that might allow for their application as self-curing bone cements, exhibiting several advantages with respect to other commercially available bone cements.

Mechanical and rheological improvement of a calcium phosphate cement by the addition of a polymeric drug

A polymeric acrylic system supporting a derivative of the aminosalicylic acid was incorporated in a calcium phosphate cement, with the aim not only to achieve some pharmacological effects but to obtain an improvement of its mechanical and rheological properties. It is known that, besides the analgesic and anti-inflammatory properties, the salicylic group presents a calcium complexation ability. The inorganic phase of the cement consisted of alpha-tricalcium phosphate [alpha-Ca(3)(PO(4))(2)] and precipitated hydroxyapatite added as a seed. The liquid phase was an aqueous solution of Na(2)HPO(4). The polymeric drug increased the injectability of the cement. The hydrolysis of the alpha-tricalcium phosphate into calcium-deficient hydroxyapatite proceeded at a lower rate because of the addition of the polymeric drug. As a consequence, the cement hardening was slightly slower, although the final compressive strength was 25% higher. The bending strength increased from 5 to 9 MPa with the addition of the polymeric drug. The strengthening of the structure was related to the reduction of porosity and the lower size of the precipitated crystals, as observed by scanning electron microscopy.

Porous starch-based drug delivery systems processed by a microwave route

A new simple processing route to produce starch-based porous materials was developed based on a microwave baking methodology. This innovative processing route was used to obtain non-loaded controls and loaded drug delivery carriers, incorporating a non-steroid anti-inflammatory agent. This bioactive agent was selected as model drug with expectations that the developed methodology might be used for other drugs and growth factors. The prepared systems were characterized by 1H and 13C NMR spectroscopy which allow the study of the interactions between the starch-based materials and the processing components, i.e. the blowing agents. The porosity of the prepared materials was estimated by measuring their apparent density and studied by comparing drug-loaded and non-loaded carriers. The behaviour of the porous structures, while immersed in aqueous media, was studied in terms of swelling and degradation, being intimately related to their porosity. Finally, in vitro drug release studies were performed showing a clear burst effect, followed by a slow controlled release of the drug over several days (up to 10 days).

Interpolymer complexes of chitosan and polymethacrylic derivatives of salicylic acid : preparation, characterization and modification by thermal treatment

Macromolecular interpolymer complexes were prepared by blending concentrated equimolar solutions of chitosan and poly(4-N-methacrylamidobenzoic acid) and evaporation of the solvents. The products obtained presented the structure of interpolymer complexes as indicated by FTIR spectroscopy. The thermal treatment of the solid products at 120°C gives rise to a partial dehydration together with the formation of covalent amide bonds between both polymeric components. The sorption behaviour of the systems is analysed on the basis of the structure of the macromolecular systems and a consideration of Fickian behaviour for highly hydrophilic materials. The diffusion coefficients determined are dependent on the thermal treatment applied to the interpolymer complexes.

New physically adsorbed polymer coating for reproducible separations of basic and acidic proteins by capillary electrophoresis

In this work, a new physically adsorbed coating for capillary electrophoresis (CE) is presented. The coating is based on a N,N-dimethylacrylamide-ethylpyrrolidine methacrylate (DMA-EPyM) copolymer synthesized in our laboratory. The capillary coating is simple and easy to obtain as only requires flushing the capillary with a polymer aqueous solution for 2 min. It is shown that by using these coated capillaries the electrostatic adsorption of a group of basic proteins onto the capillary wall is significantly reduced allowing their analysis by CE. Moreover, the DMA-EPyM coating provides reproducible separations of the basic proteins with RSD values for migration times lower than 0.75% for the same day (n = 5) and lower than 3.90% for three different days (n = 15). Interestingly, the electrical charge of the coated capillary wall can be modulated by varying the pH of the running buffer which makes possible the analysis of basic and acidic proteins in the same capillary. The usefulness of this coating is further demonstrated via the reproducible separation of whey (i.e. acidic) proteins from raw milk. The coating protocol should be compatible with both CE in microchips and CE-MS of different types of proteins.

Surface modification tailors the characteristics of biomimetic coatings nucleated on starch-based polymers.

This work describes the influence of surface pretreatments over the nucleation and growth of an apatite layer, formed by a biomimetic process, on which a bioactive glass is used as a precursor of the calcium-phosphate (Ca-P) formation on the materials surface. SEVA-C, a corn starch-based biodegradable blend, was used as substrate. The surfaces were pretreated during various periods by: (i) physical methods, namely ultraviolet radiation (u.v.), and over exposure to ethylene oxide sterilization (EtO); and (ii) chemical methods, namely potassium hydroxide (KOH) and acetic anhydride (CH3CO)2 etchings. The surface modifications, performed before the production of the biomimetic coatings, resulted in a faster formation of Ca-P nuclei during the first stages of SBF immersion, particularly in the case of the KOH etching. In this case, it was possible to observe a decrease in the average surface roughness, as measured by laser profilometry, and an increase of the hydrophilicity of the material, which was evident from a clear increment in the water-uptake ability and quantified by contact angle measurements. With this treatment it was possible not only to reduce the induction period for the formation of a well defined and dense apatite-like layer, as observed by scanning electron microscopy (SEM), but also to improve the adhesion of the Ca-P layer to the substrate, as confirmed by the adhesion strength tests. For all the studied pre-treatments, the composition of the films, analyzed by energy dispersive spectroscopy (EDS) and identified by thin-film X-ray diffraction (TF-XRD), seems to be very similar to that of human bone apatites.

Covalent Polymer-Drug Conjugates

In this work, polymer-drugs conjugates used as drug delivery systems (DDS) are revised attending to their chemical conjugation. Namely, the classification of this type of DDS is based on the conjugation sites of the reactive groups (i.e., via end groups or pendant polymer groups). Advantages and limitations of these types of DDS are discussed through representative examples of polymer-drugs and polymer-proteins conjugates recently developed.

Application of tertiary amines with reduced toxicity to the curing process of acrylic bone cements

4-Dimethylaminobenzyl alcohol (DMOH) and 4-dimethylaminobenzyl methacrylate (DMMO) were used as the activators in the benzoyl peroxide initiated redox polymerization for the preparation of acrylic bone cement based on poly(methylmethacrylate) beads of different particle size. The residual monomer content of the cured cements was about 2 wt %, independent of the redox system used in the polymerization, indicating that the activating effect of the tertiary aromatic amines DMOH or DMMO was sufficient to reach a polymerization conversion similar to that obtained with the benzoyl peroxide (BPO) N,N-dimethyl-4-toluidine (DMT) system. The BPO/DMOH and BPO/DMMO redox systems provided exotherms of decreasing peak temperature and increasing setting time, and the cured materials presented higher average molecular weight and similar glass transition temperatures in comparison with those obtained when DMT was used as the activator. In addition, these activators are three times less toxic than the classical DMT.