Rosana Pinto - Academia.edu (original) (raw)
Papers by Rosana Pinto
ACS Applied Nano Materials
Free Radical Biology and Medicine, 2018
Free Radical Biology and Medicine, 2021
The presentation will examine the employment prospects for graduates in Science, Technology, Engi... more The presentation will examine the employment prospects for graduates in Science, Technology, Engineering and Mathematics (STEM) in the UK at first cycle, masters and PhD level from UK universities in the recent past based upon extensive data available. This will be used together with surveys of employers of STEM graduates to identify the characteristics of graduates most in demand and that make a graduate more or less employable. Chemists and Chemical Engineers are included in the study and there are very large differences in their employment prospects. The 9 UL Chemistry PhD Meeting (2ECQUL) O01
Microporous and Mesoporous Materials, 2021
Abstract Hydrogen sulphide has therapeutic functions but because it is a gas its delivery as a dr... more Abstract Hydrogen sulphide has therapeutic functions but because it is a gas its delivery as a drug poses specific difficulties. Porous materials have been emerging as serious candidates for the storage and release of small gas molecules with therapeutic effects. In this work, we study microporous (A, and Y zeolites; ETS-4 and ETS-10 titanosilicates) and mesoporous (SBA-15 with and without surface amines functionalization) materials. The experimental determination of the H2S amounts released from the porous materials in liquid phase was challenging. For this, two methodologies were used, the detection through the methylene blue reaction and by a selective electrode. In the end, considering the storage amounts, the release profile and the cytotoxicity, 4A zeolite and ETS-10 titanosilicate showed the best properties.
ChemMedChem, 2021
Nitric oxide (NO) and hydrogen sulfide (H2S) have been recognized as important signalling molecul... more Nitric oxide (NO) and hydrogen sulfide (H2S) have been recognized as important signalling molecules involved in multiple physiological functions, including wound healing. Their exogenous delivery has been established as a new route for therapies, being the topical application the nearest to commercialization. Nevertheless, the gaseous nature of these therapeutic agents and their toxicity at high levels imply additional challenges in the design of effective delivery systems, including the tailoring of their morphology and surface chemistry to get controllable release kinetics and suitable lifetimes. This review highlights the increasing interest in the use of these gases in wound healing applications by presenting the various potential strategies in which NO and/or H2S are the main therapeutic agents, with focus on their conceptual design, release behaviour and therapeutic performance. These strategies comprise the application of several types of nanoparticles, polymers, porous materials, and composites as new releasing carriers of NO and H2S, with characteristics that will facilitate the application of these molecules in the clinical practice.
Molecules, 2020
The development of solid materials that deliver nitric oxide (NO) are of interest for several the... more The development of solid materials that deliver nitric oxide (NO) are of interest for several therapeutic applications. Nevertheless, due to NO’s reactive nature, rapid diffusion and short half-life, reporting their NO delivery characteristics is rather complex. The full knowledge of this parameter is fundamental to discuss the therapeutic utility of these materials, and thus, the NO quantification strategy must be carefully considered according to the NO-releasing scaffold type, to the expected NO-releasing amounts and to the medium of quantification. In this work, we explore and discuss three different ways of quantifying the release of NO in different biological fluids: haemoglobin assay, Griess assay and NO electrochemical detection. For these measurements, different porous materials, namely zeolites and titanosilicates were used as models for NO-releasing platforms. The oxyhaemoglobin assay offers great sensitivity (nanomolar levels), but it is only possible to monitor the NO r...
Angewandte Chemie International Edition, 2020
Materials for the controlled release of nitric oxide (NO) are of interest for therapeutic applica... more Materials for the controlled release of nitric oxide (NO) are of interest for therapeutic applications. However, to date, many suffer from toxicity and stability issues, as well as poor performance. Herein, we propose a new NO adsorption/ release mechanism through the formation of nitrites on the skeleton of a titanium-based metal-organic framework (MOF) that we named MIP-177, featuring a suitable set of properties for such an application: (i) high NO storage capacity (3 mmol mg À1 solid), (ii) excellent biocompatibility at therapeutic relevant concentrations (no cytotoxicity at 90 mg mL À1 for wound healing) due to its high stability in biological media (< 9 % degradation in 72 hours) and (iii) slow NO release in biological media (% 2 hours for 90 % release). The prospective application of MIP-177 is demonstrated through NO-driven control of mitochondrial respiration in cells and stimulation of cell migration, paving the way for the design of new NO delivery systems for wound healing therapy.
Materials Science and Engineering: C, 2019
The clinical demand for bone scaffolds as an alternative strategy for bone grafting has increased... more The clinical demand for bone scaffolds as an alternative strategy for bone grafting has increased exponentially and, up to date, numerous formulations have been proposed to regenerate the bone tissue. However, most of these structures lack at least one of the fundamental/ideal properties of these materials (e.g., mechanical resistance, interconnected porosity, bioactivity, biodegradability, etc.). In this work, we developed innovative composite scaffolds, based on crosslinked chitosan with glutaraldehyde (GA), combined with different atomized calcium phosphates (CaP) granules - hydroxyapatite (HA) or biphasic mixtures of HA and β - tricalcium phosphate (β-TCP), with improved biomechanical behavior and enhanced biological response. This innovative combination was designed to improve the scaffolds' functionality, in which GA improved chitosan mechanical strength and stability, whereas CaP granules enhanced the scaffolds' bioactivity and osteoblastic response, further reinforcing the scaffolds' structure. The biological assessment of the composite scaffolds showed that the specimens with 0.2% crosslinking were the ones with the best biological performance. In addition, the inclusion of biphasic granules induced a trend for increase osteogenic activation, as compared to the addition of HA granules. In conclusion, scaffolds produced in the present work, both with HA granules or the biphasic ones, and with low concentrations of GA, have shown adequate properties and enhanced biological performance, being potential candidates for application in bone tissue engineering.
Nitric Oxide, 2019
Nitric oxide (NO) presents innumerable biological roles, and its exogenous supplementation for th... more Nitric oxide (NO) presents innumerable biological roles, and its exogenous supplementation for therapeutic purposes has become a necessity. Some nanoporous materials proved to be potential vehicles for NO with high storage capacity. However, there is still a lack of information about their efficiency to release controlled NO and if they are biocompatible and biologically stable. In this work, we address this knowledge gap starting by evaluating the NO release and stability under biological conditions and their toxicity with primary keratinocyte cells. Titanosilicates (ETS-4 and ETS-10 types) and clay-based materials were the materials under study, which have shown in previous studies suitable NO gas adsorption/release rates. ETS-4 proved to be the most promising material, combining good biocompatibility at 180 µg/mL, stability and slower NO release. ETS-10 and ETAS-10 showed the best biocompatibility at the same concentration and, in the case of clay-based materials, CoOS is the least toxic of those tested and the one that releases the highest NO amount. The potentiality of these new NO donors to regulate biological functions was assessed next by controlling the mitochondrial respiration and the cell migration. NO-loaded ETS-4 regulates O 2 consumption and cell migration in a dose-dependent manner. For cell migration, a biphasic effect was observed in a narrow range of ETS concentration, with a stimulatory effect becoming inhibitory just by doubling ETS concentration. For the other materials, no effective regulation was achieved, which highlights the relevance of the new assessment presented in this work for nanoporous NO carriers that will pave the way for further developments.
Journal of chromatographic science, Jan 24, 2017
Simple, economic and environmental friendly high-performance liquid chromatography methods for le... more Simple, economic and environmental friendly high-performance liquid chromatography methods for levofloxacin and minocycline quantification in biomimetic media were developed and validate including their stability at body temperature, an often neglected evaluation parameter. Both methods are similar only differing in the wavelength setting, i.e., for levofloxacin and minocycline quantification the UV detection was set at 284 and at 273 nm, respectively. The separation of both antibiotics was achieved using a reversed-phase column and a mobile phase consisting of acetonitrile and water (15:85) with 0.6% triethylamine, adjusted to pH 3. As an internal standard for levofloxacin quantification, minocycline was used and vice versa. The calibration curves for both methods were linear (r = 0.99) over a concentration range of 0.3-16 μg/mL and 0.5-16 μg/mL for levofloxacin and minocycline, respectively, with precision, accuracy and recovery in agreement with international guidelines requireme...
Biomedical materials (Bristol, England), Jan 23, 2017
In the present work, it is aimed the development and biological characterization of a poly methyl... more In the present work, it is aimed the development and biological characterization of a poly methyl methacrylate (PMMA)-based minocycline delivery system, to be used as a space maintainer within craniofacial staged regenerative interventions. Developed delivery systems were characterized regarding solid state characteristics and assayed in vitro for anti-bacterial and anti-inflammatory activity, and cytocompatibility with human bone cells. Drug release profile allowed for an initial burst release and a more sustained and controlled release over time, with minimum inhibitory concentrations for the assayed and relevant pathogenic bacteria (i.e, Staphylococcus aureus, slime-producer-S. epidermidis and Escherichia coli) being easily attained in the early time points, and sustained up to 72 hours. Furthermore, an improved osteoblastic cell response - with enhancement of cell adhesion and cell proliferation - and increased anti-inflammatory activity were verified in developed systems, as co...
Acta biomaterialia, Mar 16, 2017
The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework ... more The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B3 building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M2(μ2-H2O)(μ-vitamin B3)4]·2H2O contain two crystallographic distinct divalent metal centres connected by a bridging water and carboxylate group from vitamin B3. The porous compounds have the capability of storing and releasing nitric oxide (NO) in a slow and reversible manner, with released amounts of 2.6 and 2.0μmol NOmgsolid(-1), on the Ni and Co compound, respectively. The NO release followed a convenient slow release kinetic profile in both gas and liquid phases. Haemoglobin tests demonstrated that NO is released to the medium in a biologically active form, thus suitable to trigger the desired response in biological systems. The toxicity of the samples with and without loaded NO was evaluated from cytotoxicity tests in HeLa and HEKn cells, sh...
Antibiotic-loaded bone cements are used to decrease occurrence of bone infections in cemented art... more Antibiotic-loaded bone cements are used to decrease occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants [1]. However, considering the challenge of treating device-associated infections there is a reduced number of formulations in the market. Response from the industry to medical need is still slow considering the rapid change in the infecting microbial profile and the emergence of multiresistant strains [2]. In this context, the aim of the work is to evaluate the role of lactose (L), as a porogen, on the antibiotic release from bone cement (BC). Levofloxacin (Lev) and minocycline (M) were the selected antibiotics to be individually loaded into BC due to their low cost and potential application in bone infections [3,4]. Two types of matrices were prepared: 1) Loaded with 2.5% of antibiotics (controls) and 2) Loaded with 10% lactose and 2.5% antibiotic. In vitro drug release and microbiological tests against representative strains causative of bone infections were assessed. Lactose significantly increased the release of both antibiotics. Complete minocycline release after one-week was observed (Fig.1A). Also, lactose increased 3.5-fold the levofloxacin released from BC (Fig.1B). Furthermore, microbiological studies showed that no interaction was observed between lactose and antibiotic as no decrease in drugs antimicrobial activity was observed (Table 1). Considering the results, L-BC matrix appears to be a valuable alternative to available formulations. Future work will include testing other antibiotics as well as mixtures of drugs. Fundacao para a Ciencia e Tecnologia (Portuguese government) for financial support: EXCL/CTM-NAN/0166/2012 and strategic project PEst-OE/SAU/UI4013/2011.
International Journal of Pharmaceutics, 2015
Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials... more Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials to control the occurrence of bone and joint infections. However, the inexistence of alternative antibiotics other than those already commercially available and the poor ability to bind to bone tissue hampering its biological function are still major drawbacks of ALABCs clinical application. The concept of this research work is to develop a novel bone cement (BC) drug delivery system composed by Mg- and Sr-doped calcium phosphate (CaP) particles as drug carriers loaded into a lactose-modified acrylic BC, which, to the best of our knowledge, has never been reported. CaP particles are known to promote bone ingrowth and current research is focused on using these carriers as antibiotic delivery systems for the treatment of bone infections, like osteomyelitis. Levofloxacin is a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues and increasingly being recommended to manage bone-related infections. Also, the lactose-modified BC matrix, with a more porous structure, has already proved to enhance antibiotic release from the BC inner matrix. This novel BC composite biomaterial has shown improved mechanical integrity, biocompatibility maintenance, and sustained release of levofloxacin, with concentrations over the minimum inhibitory concentration values after a 48h while maintaining antibacterial activity over an 8-week period against Staphyloccocus aureus and Staphyloccocus epidermidis, common pathogens associated with bone infections.
International Journal of Pharmaceutics, 2015
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bon... more Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management. 2015 Elsevier B.V. All rights reserved.
Microporous and Mesoporous Materials, 2021
Abstract Copper was incorporated into microporous titanosilicate ETS-4 framework via the in situ ... more Abstract Copper was incorporated into microporous titanosilicate ETS-4 framework via the in situ hydrothermal synthesis to achieve a more controlled and extended nitric oxide (NO) release profile. Exogeneous delivery of this gasotransmitter may be effective in the therapeutic setting and titanosilicates, in particular ETS-4, has already evidenced its potential as a NO carrier. Copper ions have high affinity for NO coordination and their substitution within the ETS-4 framework was confirmed by energy dispersive X-ray spectrometry (EDS). Samples were also characterized by PXRD, SEM microscopy, UV–Vis and Raman spectroscopy, TG and DSC. ETS-4Cu presents higher NO adsorption capacity (up to 4.5 mmol g−1 solid) comparing with the parent material, excellent stability in biological media and exhibit high compatibility in different cell lines, including primary keratinocytes (HEKn). Its NO release profile in biological conditions demonstrated a controlled release over at least 4 h, never achieved by any other porous materials so far. This may be reflected by its peculiar NO adsorption mechanism through the formation of stable nitro species on the framework.
Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders, 2019
Abstract The ability of porous solids to store significant amounts of small gas molecules at the ... more Abstract The ability of porous solids to store significant amounts of small gas molecules at the interior of their nanopores has been explored in recent years for the storage/release of nitric oxide (NO) for potential therapeutic applications, since this molecule plays a wide range of physiological and pathophysiological functions associated with cardiovascular homeostasis, immune response to infections, wound repair, tumor biology, and pathology. Indeed, the delivery of NO in a controllable manner only at specific sites of the human body can lead to therapies for many diseases. However, due to its short half-life, its rapid diffusion, and its high reactivity, significant challenges remain before the full potential of NO therapy is achieved. Conventional molecular donors that release NO at a known rate are well known, but their application in actual therapies has been limited since they are unstable and soluble in physiological media impairing their direct application to localized NO delivery. Thus, solid materials that deliver NO locally to the surrounding milieu may be a good solution to develop new products and therapies. Several materials have been proposed as NO-releasing systems, including polymer dressings, nanoparticle platforms, liposomes, dendrimers, and more recently porous materials. In this context, nanoporous materials are a very interesting alternative because they can store and release NO at target sites in the human body. Porous materials such as zeolites, clays, titanosilicates, and metal-organic frameworks (MOFs) with a variety of architectures and chemical compositions have been recently considered as NO donors, and this chapter contributes with an overview of the solids explored so far. The key parameters for designing an adequate structure, its mechanism for NO binding, and the first indicators of its potential therapeutic action are discussed, and possible further developments are suggested.
ACS Applied Nano Materials
Free Radical Biology and Medicine, 2018
Free Radical Biology and Medicine, 2021
The presentation will examine the employment prospects for graduates in Science, Technology, Engi... more The presentation will examine the employment prospects for graduates in Science, Technology, Engineering and Mathematics (STEM) in the UK at first cycle, masters and PhD level from UK universities in the recent past based upon extensive data available. This will be used together with surveys of employers of STEM graduates to identify the characteristics of graduates most in demand and that make a graduate more or less employable. Chemists and Chemical Engineers are included in the study and there are very large differences in their employment prospects. The 9 UL Chemistry PhD Meeting (2ECQUL) O01
Microporous and Mesoporous Materials, 2021
Abstract Hydrogen sulphide has therapeutic functions but because it is a gas its delivery as a dr... more Abstract Hydrogen sulphide has therapeutic functions but because it is a gas its delivery as a drug poses specific difficulties. Porous materials have been emerging as serious candidates for the storage and release of small gas molecules with therapeutic effects. In this work, we study microporous (A, and Y zeolites; ETS-4 and ETS-10 titanosilicates) and mesoporous (SBA-15 with and without surface amines functionalization) materials. The experimental determination of the H2S amounts released from the porous materials in liquid phase was challenging. For this, two methodologies were used, the detection through the methylene blue reaction and by a selective electrode. In the end, considering the storage amounts, the release profile and the cytotoxicity, 4A zeolite and ETS-10 titanosilicate showed the best properties.
ChemMedChem, 2021
Nitric oxide (NO) and hydrogen sulfide (H2S) have been recognized as important signalling molecul... more Nitric oxide (NO) and hydrogen sulfide (H2S) have been recognized as important signalling molecules involved in multiple physiological functions, including wound healing. Their exogenous delivery has been established as a new route for therapies, being the topical application the nearest to commercialization. Nevertheless, the gaseous nature of these therapeutic agents and their toxicity at high levels imply additional challenges in the design of effective delivery systems, including the tailoring of their morphology and surface chemistry to get controllable release kinetics and suitable lifetimes. This review highlights the increasing interest in the use of these gases in wound healing applications by presenting the various potential strategies in which NO and/or H2S are the main therapeutic agents, with focus on their conceptual design, release behaviour and therapeutic performance. These strategies comprise the application of several types of nanoparticles, polymers, porous materials, and composites as new releasing carriers of NO and H2S, with characteristics that will facilitate the application of these molecules in the clinical practice.
Molecules, 2020
The development of solid materials that deliver nitric oxide (NO) are of interest for several the... more The development of solid materials that deliver nitric oxide (NO) are of interest for several therapeutic applications. Nevertheless, due to NO’s reactive nature, rapid diffusion and short half-life, reporting their NO delivery characteristics is rather complex. The full knowledge of this parameter is fundamental to discuss the therapeutic utility of these materials, and thus, the NO quantification strategy must be carefully considered according to the NO-releasing scaffold type, to the expected NO-releasing amounts and to the medium of quantification. In this work, we explore and discuss three different ways of quantifying the release of NO in different biological fluids: haemoglobin assay, Griess assay and NO electrochemical detection. For these measurements, different porous materials, namely zeolites and titanosilicates were used as models for NO-releasing platforms. The oxyhaemoglobin assay offers great sensitivity (nanomolar levels), but it is only possible to monitor the NO r...
Angewandte Chemie International Edition, 2020
Materials for the controlled release of nitric oxide (NO) are of interest for therapeutic applica... more Materials for the controlled release of nitric oxide (NO) are of interest for therapeutic applications. However, to date, many suffer from toxicity and stability issues, as well as poor performance. Herein, we propose a new NO adsorption/ release mechanism through the formation of nitrites on the skeleton of a titanium-based metal-organic framework (MOF) that we named MIP-177, featuring a suitable set of properties for such an application: (i) high NO storage capacity (3 mmol mg À1 solid), (ii) excellent biocompatibility at therapeutic relevant concentrations (no cytotoxicity at 90 mg mL À1 for wound healing) due to its high stability in biological media (< 9 % degradation in 72 hours) and (iii) slow NO release in biological media (% 2 hours for 90 % release). The prospective application of MIP-177 is demonstrated through NO-driven control of mitochondrial respiration in cells and stimulation of cell migration, paving the way for the design of new NO delivery systems for wound healing therapy.
Materials Science and Engineering: C, 2019
The clinical demand for bone scaffolds as an alternative strategy for bone grafting has increased... more The clinical demand for bone scaffolds as an alternative strategy for bone grafting has increased exponentially and, up to date, numerous formulations have been proposed to regenerate the bone tissue. However, most of these structures lack at least one of the fundamental/ideal properties of these materials (e.g., mechanical resistance, interconnected porosity, bioactivity, biodegradability, etc.). In this work, we developed innovative composite scaffolds, based on crosslinked chitosan with glutaraldehyde (GA), combined with different atomized calcium phosphates (CaP) granules - hydroxyapatite (HA) or biphasic mixtures of HA and β - tricalcium phosphate (β-TCP), with improved biomechanical behavior and enhanced biological response. This innovative combination was designed to improve the scaffolds' functionality, in which GA improved chitosan mechanical strength and stability, whereas CaP granules enhanced the scaffolds' bioactivity and osteoblastic response, further reinforcing the scaffolds' structure. The biological assessment of the composite scaffolds showed that the specimens with 0.2% crosslinking were the ones with the best biological performance. In addition, the inclusion of biphasic granules induced a trend for increase osteogenic activation, as compared to the addition of HA granules. In conclusion, scaffolds produced in the present work, both with HA granules or the biphasic ones, and with low concentrations of GA, have shown adequate properties and enhanced biological performance, being potential candidates for application in bone tissue engineering.
Nitric Oxide, 2019
Nitric oxide (NO) presents innumerable biological roles, and its exogenous supplementation for th... more Nitric oxide (NO) presents innumerable biological roles, and its exogenous supplementation for therapeutic purposes has become a necessity. Some nanoporous materials proved to be potential vehicles for NO with high storage capacity. However, there is still a lack of information about their efficiency to release controlled NO and if they are biocompatible and biologically stable. In this work, we address this knowledge gap starting by evaluating the NO release and stability under biological conditions and their toxicity with primary keratinocyte cells. Titanosilicates (ETS-4 and ETS-10 types) and clay-based materials were the materials under study, which have shown in previous studies suitable NO gas adsorption/release rates. ETS-4 proved to be the most promising material, combining good biocompatibility at 180 µg/mL, stability and slower NO release. ETS-10 and ETAS-10 showed the best biocompatibility at the same concentration and, in the case of clay-based materials, CoOS is the least toxic of those tested and the one that releases the highest NO amount. The potentiality of these new NO donors to regulate biological functions was assessed next by controlling the mitochondrial respiration and the cell migration. NO-loaded ETS-4 regulates O 2 consumption and cell migration in a dose-dependent manner. For cell migration, a biphasic effect was observed in a narrow range of ETS concentration, with a stimulatory effect becoming inhibitory just by doubling ETS concentration. For the other materials, no effective regulation was achieved, which highlights the relevance of the new assessment presented in this work for nanoporous NO carriers that will pave the way for further developments.
Journal of chromatographic science, Jan 24, 2017
Simple, economic and environmental friendly high-performance liquid chromatography methods for le... more Simple, economic and environmental friendly high-performance liquid chromatography methods for levofloxacin and minocycline quantification in biomimetic media were developed and validate including their stability at body temperature, an often neglected evaluation parameter. Both methods are similar only differing in the wavelength setting, i.e., for levofloxacin and minocycline quantification the UV detection was set at 284 and at 273 nm, respectively. The separation of both antibiotics was achieved using a reversed-phase column and a mobile phase consisting of acetonitrile and water (15:85) with 0.6% triethylamine, adjusted to pH 3. As an internal standard for levofloxacin quantification, minocycline was used and vice versa. The calibration curves for both methods were linear (r = 0.99) over a concentration range of 0.3-16 μg/mL and 0.5-16 μg/mL for levofloxacin and minocycline, respectively, with precision, accuracy and recovery in agreement with international guidelines requireme...
Biomedical materials (Bristol, England), Jan 23, 2017
In the present work, it is aimed the development and biological characterization of a poly methyl... more In the present work, it is aimed the development and biological characterization of a poly methyl methacrylate (PMMA)-based minocycline delivery system, to be used as a space maintainer within craniofacial staged regenerative interventions. Developed delivery systems were characterized regarding solid state characteristics and assayed in vitro for anti-bacterial and anti-inflammatory activity, and cytocompatibility with human bone cells. Drug release profile allowed for an initial burst release and a more sustained and controlled release over time, with minimum inhibitory concentrations for the assayed and relevant pathogenic bacteria (i.e, Staphylococcus aureus, slime-producer-S. epidermidis and Escherichia coli) being easily attained in the early time points, and sustained up to 72 hours. Furthermore, an improved osteoblastic cell response - with enhancement of cell adhesion and cell proliferation - and increased anti-inflammatory activity were verified in developed systems, as co...
Acta biomaterialia, Mar 16, 2017
The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework ... more The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B3 building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M2(μ2-H2O)(μ-vitamin B3)4]·2H2O contain two crystallographic distinct divalent metal centres connected by a bridging water and carboxylate group from vitamin B3. The porous compounds have the capability of storing and releasing nitric oxide (NO) in a slow and reversible manner, with released amounts of 2.6 and 2.0μmol NOmgsolid(-1), on the Ni and Co compound, respectively. The NO release followed a convenient slow release kinetic profile in both gas and liquid phases. Haemoglobin tests demonstrated that NO is released to the medium in a biologically active form, thus suitable to trigger the desired response in biological systems. The toxicity of the samples with and without loaded NO was evaluated from cytotoxicity tests in HeLa and HEKn cells, sh...
Antibiotic-loaded bone cements are used to decrease occurrence of bone infections in cemented art... more Antibiotic-loaded bone cements are used to decrease occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants [1]. However, considering the challenge of treating device-associated infections there is a reduced number of formulations in the market. Response from the industry to medical need is still slow considering the rapid change in the infecting microbial profile and the emergence of multiresistant strains [2]. In this context, the aim of the work is to evaluate the role of lactose (L), as a porogen, on the antibiotic release from bone cement (BC). Levofloxacin (Lev) and minocycline (M) were the selected antibiotics to be individually loaded into BC due to their low cost and potential application in bone infections [3,4]. Two types of matrices were prepared: 1) Loaded with 2.5% of antibiotics (controls) and 2) Loaded with 10% lactose and 2.5% antibiotic. In vitro drug release and microbiological tests against representative strains causative of bone infections were assessed. Lactose significantly increased the release of both antibiotics. Complete minocycline release after one-week was observed (Fig.1A). Also, lactose increased 3.5-fold the levofloxacin released from BC (Fig.1B). Furthermore, microbiological studies showed that no interaction was observed between lactose and antibiotic as no decrease in drugs antimicrobial activity was observed (Table 1). Considering the results, L-BC matrix appears to be a valuable alternative to available formulations. Future work will include testing other antibiotics as well as mixtures of drugs. Fundacao para a Ciencia e Tecnologia (Portuguese government) for financial support: EXCL/CTM-NAN/0166/2012 and strategic project PEst-OE/SAU/UI4013/2011.
International Journal of Pharmaceutics, 2015
Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials... more Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials to control the occurrence of bone and joint infections. However, the inexistence of alternative antibiotics other than those already commercially available and the poor ability to bind to bone tissue hampering its biological function are still major drawbacks of ALABCs clinical application. The concept of this research work is to develop a novel bone cement (BC) drug delivery system composed by Mg- and Sr-doped calcium phosphate (CaP) particles as drug carriers loaded into a lactose-modified acrylic BC, which, to the best of our knowledge, has never been reported. CaP particles are known to promote bone ingrowth and current research is focused on using these carriers as antibiotic delivery systems for the treatment of bone infections, like osteomyelitis. Levofloxacin is a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues and increasingly being recommended to manage bone-related infections. Also, the lactose-modified BC matrix, with a more porous structure, has already proved to enhance antibiotic release from the BC inner matrix. This novel BC composite biomaterial has shown improved mechanical integrity, biocompatibility maintenance, and sustained release of levofloxacin, with concentrations over the minimum inhibitory concentration values after a 48h while maintaining antibacterial activity over an 8-week period against Staphyloccocus aureus and Staphyloccocus epidermidis, common pathogens associated with bone infections.
International Journal of Pharmaceutics, 2015
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bon... more Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management. 2015 Elsevier B.V. All rights reserved.
Microporous and Mesoporous Materials, 2021
Abstract Copper was incorporated into microporous titanosilicate ETS-4 framework via the in situ ... more Abstract Copper was incorporated into microporous titanosilicate ETS-4 framework via the in situ hydrothermal synthesis to achieve a more controlled and extended nitric oxide (NO) release profile. Exogeneous delivery of this gasotransmitter may be effective in the therapeutic setting and titanosilicates, in particular ETS-4, has already evidenced its potential as a NO carrier. Copper ions have high affinity for NO coordination and their substitution within the ETS-4 framework was confirmed by energy dispersive X-ray spectrometry (EDS). Samples were also characterized by PXRD, SEM microscopy, UV–Vis and Raman spectroscopy, TG and DSC. ETS-4Cu presents higher NO adsorption capacity (up to 4.5 mmol g−1 solid) comparing with the parent material, excellent stability in biological media and exhibit high compatibility in different cell lines, including primary keratinocytes (HEKn). Its NO release profile in biological conditions demonstrated a controlled release over at least 4 h, never achieved by any other porous materials so far. This may be reflected by its peculiar NO adsorption mechanism through the formation of stable nitro species on the framework.
Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders, 2019
Abstract The ability of porous solids to store significant amounts of small gas molecules at the ... more Abstract The ability of porous solids to store significant amounts of small gas molecules at the interior of their nanopores has been explored in recent years for the storage/release of nitric oxide (NO) for potential therapeutic applications, since this molecule plays a wide range of physiological and pathophysiological functions associated with cardiovascular homeostasis, immune response to infections, wound repair, tumor biology, and pathology. Indeed, the delivery of NO in a controllable manner only at specific sites of the human body can lead to therapies for many diseases. However, due to its short half-life, its rapid diffusion, and its high reactivity, significant challenges remain before the full potential of NO therapy is achieved. Conventional molecular donors that release NO at a known rate are well known, but their application in actual therapies has been limited since they are unstable and soluble in physiological media impairing their direct application to localized NO delivery. Thus, solid materials that deliver NO locally to the surrounding milieu may be a good solution to develop new products and therapies. Several materials have been proposed as NO-releasing systems, including polymer dressings, nanoparticle platforms, liposomes, dendrimers, and more recently porous materials. In this context, nanoporous materials are a very interesting alternative because they can store and release NO at target sites in the human body. Porous materials such as zeolites, clays, titanosilicates, and metal-organic frameworks (MOFs) with a variety of architectures and chemical compositions have been recently considered as NO donors, and this chapter contributes with an overview of the solids explored so far. The key parameters for designing an adequate structure, its mechanism for NO binding, and the first indicators of its potential therapeutic action are discussed, and possible further developments are suggested.