Loading...
9 results
Search Results
Now showing 1 - 9 of 9
- Dual on–off and off–on switchable oligoaziridine biosensorPublication . Raje, Vivek; Morgado, Patrícia I.; Ribeiro, MP.; Correia, Ilídio Joaquim Sobreira; Bonifácio, Vasco; Branco, Paula S.; Ricardo, Ana AguiarA water-soluble biocompatible aziridine-based biosensor with pendant anthracene units was synthesized by radicalar polymerization of N-substituted aziridines in supercritical carbon dioxide. The binding ability of the sensor towards a series of metal ions was examined by comparing the fluorescence intensities of the solutions before and after the addition of 100 equivalents of a solution of the metal ion chloride salt. A fast, simple and highly optical sensitive dual behavior, “off–on” and “on–off” response, was observed after the biosensor was exposed to the metal cations in aqueous solution. Zinc presented the highest fluorescence enhancement (turn-on) and copper presented the highest fluorescence quenching (turn-off). The response time was found to be instantaneous and the detection limit was achieved even in the presence of excess metal cation competitors. By using immunofluorescence microscopy it was also shown that oligoaziridine acts as an “on–off” probe through highly sensitive (detection limit of 1.6 nM), selective and reversible binding to copper anions under physiologic conditions using living Human Fibroblast cells. The stoichiometry for the reaction of the biosensor with Cu2+ was determined by a Job plot and indicates the formation of an oligoaziridine-Cu2+ 1:2 adduct.
- Poly(vinyl alcohol)/chitosan asymmetrical membranes: Highly controlled morphology toward the ideal wound dressingPublication . Morgado, Patrícia I.; Lisboa, Pedro; Ribeiro, MP.; Miguel, Sónia P.; Simões, Pedro; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarAsymmetrical membranes have been reported as ideal wound dressings for skin regeneration. The usual methods (dry/wet-phase inversion) to produce those specific membranes are time consuming, and in majority of the cases demand the use of harmful organic solvents. In this study, supercritical carbon dioxide (scCO2)-assisted phase inversion method was applied to prepare poly(vinyl alcohol)/chitosan (PVA/CS) asymmetrical membranes. This technique can tailor the final structure of the dressing by tuning the processing conditions allowing the development of high porous materials with optimized morphology, mechanical properties and hydrophilicity. The PVA/CS dressings produced are recovered in a dry state but can form a hydrogel due to their high water uptake ability maintaining the moisturized environment needed for wound healing. The dressing presents a top thin layer of about 15 µm that allows gaseous exchange while barricading the penetration of microorganisms, and a sponge bottom layer that is able to remove excess exudates. A mathematical model based on Fick׳s second law of diffusion was developed to describe the pharmacokinetic release profile of a small drug (ibuprofen) from the swollen membrane in physiological conditions that mimic the wound. In vitro studies revealed that the dressings had excellent biocompatibility and biodegradation properties adequate for skin wound healing.
- Biocompatible Polyurea Dendrimers with pH‐Dependent FluorescencePublication . Restani, Rita; Morgado, Patrícia I.; Ribeiro, MP.; Correia, I.J.; Ricardo, Ana Aguiar; Bonifácio, VascoBiocompatible and biodegradable water‐soluble dendrimers comprising ureas within the interior and amino groups on the periphery were synthesized in supercritical carbon dioxide (dendrimer of generation 1 shown in picture). This novel class of dendrimers shows a pH‐dependent intrinsic blue fluorescence at very low concentrations, which makes them potential polymeric fluorescent cell markers.
- Characterization of the Mechanical and Biological Properties of a New Alumina ScaffoldPublication . Batista, Patrícia Sofia Pinhanços; Rodrigues, Miguel; Silva, Daniela; Morgado, Patrícia I.; Henriques, J.; Almeida, Maria; Silva, Abílio P.; Correia, Ilídio Joaquim SobreiraPurpose: In this work, an alumina scaffold was produced through a new method to be used in a near future as a bone substitute. Methods: In vitro and in vivo studies were performed in order to characterize the mechanical and biological properties of the scaffold. Results: the results obtained showed that this scaffold has high mechanical resistance and a porous surface that allows human osteoblast cells to adhere and proliferate. the in vivo studies revealed no systemic reaction. Conclusions: the alumina scaffold produced herein has the mechanical and biological properties that are compatible with its application in bone therapy.
- Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healingPublication . Ribeiro, MP.; Morgado, Patrícia I.; Miguel, Sónia P.; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim SobreiraSkin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine.
- Asymmetric membranes as ideal wound dressings: An overview on production methods, structure, properties and performance relationshipPublication . Morgado, Patrícia I.; Ricardo, Ana Aguiar; Correia, I.J.Healing a wound is a process that comprises sequential steps aimed to restore the structure and function of damaged cells and tissues. Since the antiquity, to promote an effective wound healing, different materials have been used to cover the wound. Nowadays, dressings that are able to mimic the structure and composition of skin are specifically designed to exhibit several required functions. To cope with this demand, different wound dressings have been produced using conventional techniques, during the last two decades. Among them, asymmetric ones present a dense top layer to protect the wound from physical damage and pathogen penetration and an inner porous layer that allows the exudates absorption, keeping the moisturized environment needed for effective skin regeneration. However, the production methods used so far, wet- and dry/wet-phase inversion techniques, present some limitations such as the use of toxic organic solvents, the lack of polymers variety and are very time-consuming. In addition, taking into account the worldwide economic status, sustainable procedures, like supercritical carbon dioxide (scCO2) – assisted phase inversion and electrospinning techniques can be adopted to produce suitable dressings for wound-management. Herein, a critical review of the methods used to produce asymmetric membranes is presented, highlighting the different properties that can be enhanced for wound healing purposes.
- Development of different drug delivery systems for skin regenerationPublication . Morgado, Patrícia Isabel da Cruz; Correia, Ilídio Joaquim SobreiraThe human body has different fluids that are hostile environments for biologically active molecules. To overcome this arbitrary, several drug delivery systems have been developed. These systems not only protect all unstable biological active compounds from enzymatic degradation in the human body but also allow a sustained and targeted release of drugs. They contribute for decreasing drug dose required to achieve the desired therapeutic effect. Hydrogels, with their important characteristics, have been widely used in the development of these systems however, the quantity of drug loaded into them may be limited and the high water content of these polymeric matrices often results in relatively rapid drug release profiles. Nevertheless, due to their good physical and biological properties, hydrogels have been extensively used in the treatment of skin injuries. In order to take advantage of hydrogels for drug delivery and wound healing, different systems (nano and micrometric) have been developed and incorporated into hydrogels matrices. Nano and micro systems exhibit high encapsulation efficiencies of drugs and allow its release for a long period of time. Thus, the main goals of this master thesis work plan were to develop micrometric systems based on chitosan, alginate and a dextran hydrogel, and characterize their applicability in the treatment of skin injuries. Initially, the carriers were characterized according to their size, geometry, swelling behavior and biocompatibility. In vitro release studies allow us to analyze the release profile of a model protein (bovine serum albumin) when encapsulated into the microparticles. The same studies were done for microparticles loaded into a dextran hydrogel. Co-relating the swelling studies with the in vitro protein release studies a mathematical model based on the theory of hindered transport of large solutes in hydrogels was developed for theoretically describing the process of protein release. All the experimental results were interpreted with the aid of the developed model. Moreover it can contribute to decrease the number of experimental studies, reducing costs and saving time for the carrier development. After that, growth factors (vascular endothelial growth factor and endothelial growth factor) were encapsulated into chitosan microparticles that were then loaded into the dextran hydrogel. Subsequently in vivo studies were performed to characterize the applicability of the dextran hydrogel loaded with chitosan microparticles containing growth factors in wound healing. The in vitro and in vivo studies demonstrated that the developed carriers are biocompatible, accelerate the wound healing process and can be used to deliver other bioactive agents.
- Development of 2-(dimethylamino)ethyl methacrylate-based molecular recognition devices for controlled drug delivery using supercritical fluid technologyPublication . Silva, Mara da; Viveiros, Raquel; Morgado, Patrícia I.; Ricardo, Ana Aguiar; Correia, Ilídio Joaquim Sobreira; Casimiro, TeresaThis work reports the development of a novel potential body-friendly oral drug delivery system, which consists of a biocompatible molecularly imprinted polymer (MIP), with pH sensitive character and low cross-linking degree (20.2 wt%), synthesized and processed in supercritical carbon dioxide. The MIP is synthesized using 2-(dimethylamino)ethyl methacrylate (DMAEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker, and ibuprofen as molecular recognition template. The imprinted matrix was able to show a higher affinity towards ibuprofen than its corresponding non-imprinted polymer (NIP) meaning that the molecular imprinting in scCO2 was efficient even using a low crosslinking degree. MIP showed a significant molecular recognition towards the template, presenting higher drug uptake ability in the supercritical impregnation step, loading 33.1 wt% of ibuprofen compared to only 10.2 wt% for the NIP polymer. In vitro drug release experiments, simulating an oral administration, showed different release profiles at pH 2.2 and pH 7.4. Zeta potential measurements were performed to both MIP and NIP showing that the imprinting process has a significant influence on the charge of the polymeric particles. Cytotoxicity assays performed with human colorectal carcinoma-derived Caco-2 cells demonstrated that the polymers are biocompatible and could be potentially used in drug delivery applications.
- Ibuprofen loaded PVA/chitosan membranes: A highly efficient strategy towards an improved skin wound healingPublication . Morgado, Patrícia I.; Miguel, Sónia P.; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarDuring wound healing, an early inflammation can cause an increase of the wound size and the healing process can be considerably belated if a disproportionate inflammatory response occurs. (S)-ibuprofen (IBP), a non-steroidal anti-inflammatory agent, has been used for muscle healing and to treat venous leg ulcers, but its effect in skin wound healing has not been thoroughly studied thus far. Herein, IBP-β-cyclodextrins carriers were designed to customise the release profile of IBP from poly(vinyl alcohol)/chitosan (PVA/CS) dressings in order to promote a faster skin regeneration. The dressings were produced using supercritical carbon dioxide (scCO2)-assisted technique. In vitro IBP release studies showed that β-cyclodextrins allowed a controlled drug release from the hydrogels which is crucial for their application in wound management. Moreover, the in vivo assays revealed that the presence of PVA/CS membranes containing IBP-β-cyclodextrins carriers avoided scab formation and an excessive inflammation, enabling an earlier skin healing.