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Biomedical subjects

António M Cunha

Publications and source records attributed to António M Cunha.

7 recordsLinked to original sources

Determination of diffusion coefficients of glycerol and glucose from starch based thermoplastic compounds on simulated physiological solution.

Blends of corn starch with poly(ethylene-vinylalcohol) copolymer (SEVA-C) have been studied and reported as biodegradable. These materials are known to be sensitive to enzymatic action, evidencing a degradation of the starch phase in alpha-amylase assays. However, from the physical-chemical point of view the degradation of the blend is mainly associated with the leaching of glycerol, since other compounds are not released and no carbohydrates were found in the degradation solution. Based on these results, the present work attempts to determinate the respective diffusion coefficients. Four different experiments were performed, using samples with different thicknesses that were immersed in a simulated physiological solution. High performance liquid chromatography (HPLC) was used to separate the sugar derivatives and glycerol from the degradation solutions. The obtained data were fitted to an empirical model to allow the estimation of the diffusion coefficient for glycerol and glucose, based on the analytical solution for Fick's law of diffusion, and a good agreement was found (R(2) equals approximately 1). The glycerol leaches quickly out during the first few days of immersion, stabilizing thereafter, presenting greater diffusion coefficients for thicker samples. As the quantity of saccharides in the solution remains almost invariable along the experiments, this work also confirms that the degradation process is difficult without the action of enzymes.

Biocompatible Materials↗

Controlled delivery achieved with bi-layer matrix devices produced by co-injection moulding.

The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device.

Biocompatible Materials↗

Enzymatic degradation of starch-based thermoplastic compounds used in protheses: identification of the degradation products in solution.

Apart from favourable physico-chemical and mechanical properties, the most important requirement for a biodegradable polymer to be used in medical applications is its biocompatibility and the non-cytotoxicity of its degradation products. Their combined effect should assure the safe material degradation under controlled kinetics. The present work analyses the degradation behaviour of blends of corn starch with poly(ethylene-vinyl alcohol) copolymer (SEVA-C). The characterization included long-term degradation trials on simulated physiological solution with alpha-amylase up to 200 days. The degradation solutions were analysed by several techniques. High-performance liquid chromatography (HPLC) and colorimetric methods were used to monitor the liberation of carbohydrate as a consequence of starch hydrolysis by alpha-amylase. The hydration degree was followed by thermogravimetric analysis (TGA). Several degradation products such as carbohydrates ranging from C6 to C18 were identified. After alpha-amylase action, biodegradation was more pronounced in the first 100 days, after which the biodegradation rate decreased probably due to the structure and porosity of the material. The action of alpha-amylase solely led to the starch degradation, in contrast with other assays without enzymes where no carbohydrates were found in the degradation solutions.

Carbohydrate Metabolism↗

Changes in morphology of starch-based prothestic thermoplastic material during enzymatic degradation.

This work evaluates the structural changes of an interpenetrated starch thermoplastic blend withstanding different enzymatic alpha-amylase degradation periods (up to 200 days), and establishes the relationships between the kinetics degradation rate and the structure of the material. It characterises the different stages of the enzymatic degradation process on starch/ethylenevinyl-alcohol blends, based on the attack of the connected starch domains that can be accessed by the enzymatic solution. The completely encapsulated starch particles remain practically unchanged. Furthermore, it was also found that the enzymatic degradation process was limited after 100 days of immersion. In order to understand such phenomenon several techniques were used, namely differential scanning calorimetry, contact-angle measurements, high-performance liquid chromatography, Fourier transform infrared spectrometry, scanning electron microscopy and atomic force microscopy. The materials were evaluated with respect to the enzymatic degradation rate, surface morphology and degradation behaviour. The results show that the ethylene-vinylalcohol phase wraps the starch domains, preventing the respective degradation. Consequently, the degraded material in the solution comes only from the starch particles that could be reached by the enzyme.

Alcohols↗

Plasma- and chemical-induced graft polymerization on the surface of starch-based biomaterials aimed at improving cell adhesion and proliferation.

Plasma and chemical induced graft polymerization of acrylic monomers on starch-based biomaterials has been performed with the aim to improve cell adhesion and proliferation on the surface of the polymers, in order to adequate their properties for bone tissue engineering scaffolding applications. Plasma and chemical surface activation was aimed to induce the polymerization of acrylic polar monomers being carried out by applying a radio frequency plasma and expose the samples to a mixture of Ar/O2, or by immersion in a H2O2/(NH4)2S2O8 solution with UV radiation, respectively. Both procedures were followed by the graft polymerization of the corresponding monomers. Polymer grafting was analyzed by Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and by contact angle measurements. Properties such as mechanical performance, swelling degree, and degradation behavior, as well as bioactivity, have been studied and compared for the different activation methods. Finally, preliminary cell adhesion and proliferation tests were performed, using goat bone marrow cells, showing a remarkable improvement with respect to original non-surface modified starch-based biomaterials.

Journal Article↗

Effect of crosslinking, thermal treatment and UV irradiation on the mechanical properties and in vitro degradation behavior of several natural proteins aimed to be used in the biomedical field.

Gelatine (GEL), soy (SI), casein (CAS) and sodium-caseinate (NaCAS) solutions were cast to produce protein films. All the proteins were chemically modified by adding glyoxal to the film-forming solutions in amounts varying from 0 to 0.9% (w/w based on the protein content). After casting, the same films were also submitted to a heat treatment performed at 80 degrees C or UV irradiation. The effect of those chemical/physical modifications on the mechanical properties and on the hydrolytic stability of the protein films was evaluated. As a result, a large variety of protein films with different mechanical properties and degradation profiles were developed. CAS and NaCAS even when chemically/physically modified do not resist to hydrolysis longer than 2 weeks. GEL, only when chemically modified with glyoxal, become water resistant. Due to its hydrolytic stability, SI become a very attractive material for biomedical applications where long term treatments are a requisite.

Journal Article↗

Soy matrix drug delivery systems obtained by melt-processing techniques.

The aim of this study was to develop new soy protein drug delivery matrix systems by melt-processing techniques, namely, extrusion and injection moulding. The soy matrix systems with an encapsulated drug (theophylline, TH) were previously compounded by extrusion performed at two different pH values, (i) pH 4 (SIpDtp) and (ii) pH 7 (SIDtp), and further injection-moulded into a desired shape. During the extrusion process the matrixes SIDtp were also cross-linked with glyoxal (0.6X-SIDtp) and reinforced with a bioactive filler, hydroxylapatite (SI-HADtp). The obtained mouldings were used to study the drug-release mechanisms from the plastic soy-TH matrixes. In an isotonic saline solution (ISS) buffered at pH 5.0 (200 mM acetate buffer), the resulting release kinetics could be described using the Fick's second law of diffusion. Because the diffusion coefficients were found to be constant and the boundary conditions to be stationary, these systems are drug-diffusion controlled. Conversely, the dominant phenomena in an isotonic saline solution buffered at pH 7.4 (200 mM Tris/HCl buffer) are more complex. In fact, because of the higher polymer solubility, the resulting matrix is time-variant. So, the drug release is affected by swelling, drug diffusion, and polymer dissolution, being faster when compared to ISS-200 mM acetate buffer, pH 5.0. The changes in the formulation composition affecting the correspondent release rates were also investigated. At pH 7.4, increasing the cross-linking degree of the polymer matrix (via reaction with glyoxal or heat treatment) or decreasing the net charge (extruding at pH near its isoelectric point) led to lower release rates. The incorporation of ceramic filler caused the opposite effect. Because of the low solubility of the matrix at pH 5.0, no significant variations were detected with variations in the selected formulations. These systems, based on a nonstandard protein-based material, seem to be very promising to be used as carriers for drug delivery.

Biocompatible Materials↗