M.H. Gil

Development of novel alginate based hydrogel films for wound healing applications.

Alginate and Aloe vera are natural materials widely investigated and used in the biomedical field. In this research work, thin hydrogel films composed by alginate and Aloe vera gel in different proportions (95:5, 85:15 and 75:25, v/v) were prepared and characterized. The films were evaluated regarding the light transmission behavior, contact angle measurements, and chemical, thermal and mechanical properties. These thin hydrogel films, prepared by crosslinking reaction using 5% calcium chloride solution, were also investigated relatively to their water solubility and swelling behavior. Results showed that Aloe vera improved the transparency of the films, as well their thermal stability. The developed films present adequate mechanical properties for skin applications, while the solubility studies demonstrated the insolubility of the films after 24h of immersion in distilled water. The water absorption and swelling behavior of these films were greatly improved by the increase in Aloe vera proportion.

Preparation and chemical and biological characterization of a pectin/chitosan polyelectrolyte complex scaffold for possible bone tissue engineering applications

In this work, porous scaffolds obtained from the freeze-drying of pectin/chitosan polyelectrolyte complexes were prepared and characterized by FTIR, SEM and weight loss studies. Additionally, the cytotoxicity of the prepared scaffolds was evaluated in vitro, using human osteoblast cells. The results obtained showed that cells adhered to scaffolds and proliferated. The study also confirmed that the degradation by-products of pectin/chitosan scaffold are noncytotoxic.

Physical and chemical characterisation of some silicas and silica derivatives

An extensive study of four types of porous silica supports has been performed, with particular emphasis on their physical and morphological characteristics. These silicas were modified by reacting the surface silanol groups present with either 3-(trimethoxysilyl)propylmethacrylate or 3-glycidoxypropyltrimethoxysilane or 3-aminopropyltriethoxysilane, to produce derivatives with suitable functional groups for further utilisation in the immobilisation of biological compounds. The silicas and their derivatives used were fully characterised with regard to particle size distribution (laser light scattering), specific surface area (BET method), pore size distribution (gas adsorption and mercury porosimetry), density (helium pycnometry), yield of grafting (TGA) and chemical composition (FTIR/DRIFT).

Impregnation of an intraocular lens for ophthalmic drug delivery.

In this work the possibility of impregnating P(MMA-EHA-EGDMA) with flurbiprofen using a clean and environmentally friendly technology, namely supercritical fluid technology was evaluated. P(MMA-EHA-EGDMA) has been proposed as a promising matrix to be used for intraocular delivery of anti-inflammatory drugs used in eye surgery and flurbiprofen is a non-steroidal anti-inflammatory agent. Fundamental studies like, the solubility of the drug in carbon dioxide, as well as the sorption degree of this polymeric matrix in the presence of carbon dioxide have been previously carried out. The aim of this research was to evaluate the effects of these two variables in the impregnation process. Different experimental conditions were tested and the results obtained suggest that the best impregnating conditions for this system are low temperatures and pressures, which at the same time correspond to a lower solubility of the drug in the supercritical fluid and a low swelling of the polymeric matrix. Experiments performed also indicate that the batch impregnation process leads to higher yields of impregnation and according to the release profiles obtained the drug can be released from the matrix up to three months, which presents great advantages for post-surgical treatments.

Surface grafting of a thermoplastic polyurethane with methacrylic acid by previous plasma surface activation and by ultraviolet irradiation to reduce cell adhesion

The material performance, in a biological environment, is mainly mediated by its surface properties and by the combination of chemical, physical, biological, and mechanical properties required, for a specific application. In this study, the surface of a thermoplastic polyurethane (TPU) material (Elastollan(®)1180A50) was activated either by plasma or by ultra-violet (UV) irradiation. After surface activation, methacrylic acid (MAA) was linked to the surface of TPU in order to improve its reactivity and to reduce cell adhesion. Grafted surfaces were evaluated by X-ray photoelectron spectroscopy (XPS), by atomic force microscopy (AFM) and by contact angle measurements. Blood compatibility studies and cell adhesion tests with human bone marrow cells (HBMC) were also performed. If was found that UV grafting method led to better results than the plasma activation method, since cell adhesion was reduced when methacrylic acid was grafted to the TPU surface by UV.

Photocrosslinkable biodegradable responsive hydrogels as drug delivery systems

Recently, controlled release from biocompatible materials has received much attention for biomedical applications. Due to their biocompatibility and biodegradability, glucopyranosides such as dextran appear as promising polymeric materials if one is able to regulate their rheological properties and the encapsulation/release efficiency. In this work graft polymer hydrogels from dextran and N-isopropylacrylamide (NIPAAm) were prepared and characterized. Dextran molecules were modified with 2-isocyanatoethylmethacrylate (IEMA) in order to obtain a polymer with carbon double bonds. Urethane linkages resulted from the reaction between hydroxyl groups (OH) of the dextran and isocyanate groups (NCO) of the IEMA. The obtained polymer was then crosslinked by UV irradiation in the presence of the photoinitiating agent Irgacure 2959 by CIBA. The drug Ondansetron was entrapped in the final system and its release profile was determined at 25 and 37°C. The characterization of the materials was accomplished by: ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared) spectroscopy, elemental analysis, lower critical solution temperature (LCST) determination, swelling behaviour evaluation, determination of surface energy by contact angle measurement and drug delivery profile studies.

Influence of Aloe vera on water absorption and enzymatic in vitro degradation of alginate hydrogel films.

This study investigates the influence of Aloe vera on water absorption and the in vitro degradation rate of Aloe vera-Ca-alginate hydrogel films, for wound healing and drug delivery applications. The influence of A. vera content (5%, 15% and 25%, v/v) on water absorption was evaluated by the incubation of the films into a 0.1 M HCl solution (pH 1.0), acetate buffer (pH 5.5) and simulated body fluid solution (pH 7.4) during 24h. Results show that the water absorption is significantly higher for films containing high A. vera contents (15% and 25%), while no significant differences are observed between the alginate neat film and the film with 5% of A. vera. The in vitro enzymatic degradation tests indicate that an increase in the A. vera content significantly enhances the degradation rate of the films. Control films, incubated in a simulated body fluid solution without enzymes, are resistant to the hydrolytic degradation, exhibiting reduced weight loss and maintaining its structural integrity. Results also show that the water absorption and the in vitro degradation rate of the films can be tailored by changing the A. vera content.

Tailoring the properties of gelatin films for drug delivery applications: influence of the chemical cross-linking method.

Two types of chemically cross-linked gelatin films were prepared and characterized. The first type of films was cross-linked with 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC) under heterogeneous conditions and are named Gel-E. In the second type of films, gelatin was previously functionalized with methacrylamide side groups by the reaction with methacrylic anhydride and for that is named Gel-MA. The modified gelatin was subsequently cross-linked by a photoinitiated radical polymerization. These films were characterized relatively to their degree of cross-linking, buffer uptake capacity, resistance to hydrolytic and proteolytic degradation, and mechanical and thermal properties. Results show that the employed cross-linking method, together with the degree cross-linking, dictate the final properties of the films. Gel-E films have significant lower buffer uptake capacities and higher resistance to collagenase digestion when compared to Gel-MA films. Additionally, Gel-E films exhibit higher values of stress at break and lower strains at break. Moreover, the films properties could be modified by varying the extent of the chemical cross-linking, which in turn could be controlled by varying the concentration of EDC, for the first type of films (Gel-E), or by using gelatins with different degrees of functionalization, in the case of the second type of films (Gel-MA).

In vitro and in vivo evaluation of an intraocular implant for glaucoma treatment

Implantable disks for glaucoma treatment were prepared by blending poly(ɛ-caprolactone), PCL, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) and dorzolamide. Their in vivo performance was assessed by their capacity to decrease intraocular pressure (IOP) in normotensive and hypertensive eyes. Drug mapping showed that release was complete from blend disks and the low molecular weight (MW) PCL after 1 month in vivo. The high MW PCL showed non-cumulative release rates above the therapeutic level during 3 months in vitro. In vivo, the fibrous capsule formation around the implant controls the drug release, working as a barrier membrane. Histologic analysis showed normal foreign body reaction response to the implants. In normotensive eyes, a 20% decrease in IOP obtained with the disks during 1 month was similar to Trusopt eyedrops treatment. In hypertensive eyes, the most sustained decrease was shown by the high MW PCL (40% after 1 month, 30% after 2 months). It was shown that the implants can lower IOP in sustained manner in a rabbit glaucoma model.

Design and characterization of bi-soft segmented polyurethane microparticles for biomedical application.

Bi-soft segmented poly(ester urethane urea) microparticles were prepared and characterized aiming a biomedical application. Two different formulations were developed, using poly(propylene glycol), tolylene 2,4-diisocyanate terminated pre-polymer (TDI) and poly(propylene oxide)-based tri-isocyanated terminated pre-polymer (TI). A second soft segment was included due to poly(ɛ-caprolactone) diol (PCL). Infrared spectroscopy, used to study the polymeric structure, namely its H-bonding properties, revealed a slightly higher degree of phase separation in TDI-microparticles. TI-microparticles presented slower rate of hydrolytic degradation, and, accordingly, fairly low toxic effect against macrophages. These new formulations are good candidates as non-biodegradable biomedical systems.