Percorrer por autor "Saramago, Benilde"
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- About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro studyPublication . Galante, Raquel; Paradiso, Patrizia; Moutinho, Maria Guilhermina; Fernandes, Ana Isabel; Mata, José; Matos, António; Colaço, Rogério; Saramago, Benilde; Serro, Ana Paula"The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before. Two poly-2-hydroxyethylmethacrylate based hydrogels, pHEMA-T and pHEMA-UV, were used as model materials. Levofloxaxin was chosen as model drug. The hydrogels were fully characterized in what concerns structural and physicochemical properties. PHEMA-UV revealed some superficial porosity and a lower short range order than PHEMA-T. We observe that the load and friction cycles enhanced the drug release from pHEMAUV hydrogels. The application of a simple mathematical model, which takes into account the drug dilution caused by the tear flow, showed that the enhancement of the drug release caused by blinking on this hydrogel may be relevant in in vivo conditions. Conversely, the more sustained drug release from pHEMA-T is not affected by load and friction cycles. The conclusion is that, depending on the physicochemical and microstructural characteristics of the hydrogels, blinking is a factor that may affect the amount of drug delivered to the eye by SCLs and should thus be considered."
- Antiseptic-loaded casein hydrogels for wound dressingsPublication . Garcia, Leonor Vasconcelos; Silva, Diana; Costa, Maria Madalena; Armés, Henrique; Salema-Oom, Madalena; Saramago, Benilde; Serro, Ana PaulaChronic wound treatment accounts for a substantial percentage of the medical expenses worldwide. Improving and developing novel wound care systems can potentially help to handle this problem. Wound dressings loaded with antiseptics may be an important tool for wound care, as they inhibit bacterial growth at the wound site. The goal of the present work was to investigate the potential of using casein hydrogel dressings loaded with two antiseptic drugs, Octiset® or polyhexanide, to treat chronic wounds. Casein-based hydrogels are inexpensive and have several properties that make them suitable for biomedical applications. Two types of casein were used: casein sodium salt and acid casein, with the formulations being labelled CS and C, respectively. The hydrogels were characterised with respect to their physical properties (swelling capacity, water content, morphology, mechanical resistance, and stability), before and after sterilisation, and they showed adequate values for the intended application. The hydrogels of both formulations were able to sustain controlled drug-release for, at least, 48 h. They were demonstrated to be non-irritant, highly haemocompatible, and non-cytotoxic, and revealed good antimicrobial properties against Staphylococcus aureus and Pseudomonas aeruginosa. Steam-heat sterilisation did not compromise the material’s properties. The in vivo performance of C hydrogel loaded with Octiset® was evaluated in a case study with a dog. The efficient recovery of the wounds confirms its potential as an alternative for wound treatment. To our knowledge, this is the first time that wound dressings loaded with Octiset®, one of the most efficient drugs for wound treatment, were prepared and tested.
- Asymmetry in drug permeability through the corneaPublication . Toffoletto, Nadia; Chauhan, Anuj; Alvarez-Lorenzo, Carmen; Saramago, Benilde; Serro, Ana PaulaThe permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release systems.
- Capture of opiates by ionic liquidsPublication . Restolho, José; Barroso, Mário; Dias, Mário; Afonso, Carlos A. M.; Saramago, BenildeRoom temperature ionic liquids (RTILs) are known to provide efficient extraction media for a variety of systems. In particular, their ability to remove low volatility compounds (including opiate drugs) from the surface of human hair was recently demonstrated by this team. Among many tested ILs, some exhibited high extraction efficiencies for the two studied compounds, morphine and 6-monoacetylmorphine, while others have practically zero efficiency. The aim of the present study was to further understand the special affinity of specific combinations cation/anion towards the opiate drugs, through a systematic study of a limited number of ILs: 1-ethyl-3-methylimidazolium acetate, [C2mim][OAc], 1-butyl-3-methylimidazolium acetate [C4mim][OAc], 1-hexyl-3-methylimidazolium acetate [C6mim][OAc], 1-ethanol-3-methylimidazolium tetrafluoroborate, [C2OHmim][BF4], 1-ethanol-3-methylimidazolium chloride [C2OHmim][Cl], and 1-butyl-3-methylimidazolium tetrafluoroborate, [C4mim][BF4]. Correlations between the efficiency of drug extraction from hair and the water content, surface tension and polarity of the ionic liquids (ILs) were found. The extraction efficiency increased with the IL’s water content, although in a different way for each IL/drug pair. A decrease in the surface tension during the process of drug extraction was detected only for highly efficient ILs. Efficiency was correlated with the polarity parameters defined by Kamlet and Taft: large for ILs of high acidity and low basicity (e.g. [C2OHmim][BF4]) and small for liquids with of low acidity and high basicity (e.g. [C6mim][OAc]).
- Chitosan/alginate based multilayers to control drug release fromophthalmic lensPublication . Silva, Diana; Pinto, Luís F. V.; Bozukova, Dimitriya; Santos, Luís F.; Serro, Ana Paula; Saramago, BenildeIn this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate – CaCl2)/(chitosan + glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle ≈ 0) and biocompatibility, it should avoid the use of further surface treatments to enhance the useŕs comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug.
- Controlled drug delivery from ophthalmic lensesPublication . Topete, Ana; Oliveira, Andreia; Pimenta, Andreia; Silva, Diana; Carrilho, Magda; Paradiso, Patrizia; Kumar, Prashneel; Galante, Raquel; Mata, José; Colaço, Rogério; Saramago, Benilde; Serro, Ana Paula
- Controlled release of antibiotics from vitamin E–loaded silicone-hydrogel contact lensesPublication . Paradiso, Patrizia; Serro, Ana Paula; Saramago, Benilde; Colaço, Rogério; Chauhan, AnujSymptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs. We specifically focus on increasing the release duration of levofloxacin and chlorhexidine from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS® contact lenses by incorporating vitamin E diffusion barriers. Results show that 20% of vitamin E loading in the contact lens increases the release duration of levofloxacin to 100 h and 50 h from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS®, respectively, which is a 3- and 6-fold increase, respectively, for the 2 lenses. For chlorhexidine, the increase is 2.5- and 10-fold, for the TrueEye™ and OASYS®, respectively, to 130 h and 170 h. The mass of drug loaded in the lenses can be controlled to achieve a daily release comparable to the commonly prescribed eye drop therapy. The vitamin E–loaded lenses retain all critical properties for in vivo use.
- Development, optimization, and validation of a novel extraction procedure for the removal of opiates from human hair’s surfacePublication . Restolho, José; Barroso, Mário; Saramago, Benilde; Dias, Mário; Afonso, Carlos A. M.Room temperature ionic liquids (ILs) have proved to be efficient extraction media for several systems, and their ability to capture volatile compounds from the atmosphere is well established. We report herein a contactless extraction procedure for the removal of opiate drugs from the surface of human hair. The compounds were chosen as a model drug, particularly due to their low volatility. Equal amounts of IL and hair (about 100 mg) were introduced in a customized Y-shaped vial, and the process occurred simply by heating. After testing several ILs, some of them (e.g. 1-methyl-3-ethanol-imidazolium tetrafluoroborate, phenyl-trimethyl-ammonium triflate or bis(dimethyl) diheptylguanidinium iodide) showed extraction efficiencies higher than 80% for the two studied compounds, morphine and 6-monoacetylmorphine. Using the design of experiments (DOE) approach as an optimization tool, and bearing in mind the hygroscopic properties of the ILs (in particular, 1-methyl-3-ethanol-imidazolium tetrafluoroborate), the process was optimized concerning the following variables: temperature (50–120 ºC), extraction time (8–24 h), IL amount (50–200 mg) and water content of the IL (0.01–60%). This study not only provided the optimum conditions for the process (120 ºC, 16 h, 100 mg of IL containing 40% of water), but has also showed that the water content of the IL represents the variable with the most significant effect on the extraction efficiency. Finally, we validated our method through the comparison of the results obtained by treating hair samples with the described procedure to those obtained using a standard washing method and criteria for positivity.
- Diclofenac release from a silicon based contact lens material controlled by a chitosan/alginate coatingPublication . Filipe, Helena; Silva, Diana; Pinto, Luís F. V.; Henriques, José; Bozukova, Dimitriya; Saramago, Benilde; Serro, Ana Paula
- Diffusion-based design of multi-layered ophthalmic lenses for controlled drug releasePublication . Pimenta, Andreia F. R.; Serro, Ana Paula; Paradiso, Patrizia; Saramago, Benilde; Colaço, RogérioThe study of ocular drug delivery systems has been one of the most covered topics in drug delivery research. One potential drug carrier solution is the use of materials that are already commercially available in ophthalmic lenses for the correction of refractive errors. In this study, we present a diffusion-based mathematical model in which the parameters can be adjusted based on experimental results obtained under controlled conditions. The model allows for the design of multi-layered therapeutic ophthalmic lenses for controlled drug delivery. We show that the proper combination of materials with adequate drug diffusion coefficients, thicknesses and interfacial transport characteristics allows for the control of the delivery of drugs from multi-layered ophthalmic lenses, such that drug bursts can be minimized, and the release time can be maximized. As far as we know, this combination of a mathematical modelling approach with experimental validation of non-constant activity source lamellar structures, made of layers of different materials, accounting for the interface resistance to the drug diffusion, is a novel approach to the design of drug loaded multi-layered contact lenses.
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