Loading...
14 results
Search Results
Now showing 1 - 10 of 14
- Nano‐in‐Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary DeliveryPublication . Restani, Rita; Silva, A. Sofia; Pires, Rita; Cabral, Renato; Correia, Ilídio Joaquim Sobreira; Casimiro, Teresa; Bonifácio, Vasco; Ricardo, Ana AguiarPulmonary administration offers excellent advantages over conventional drug delivery routes, including increasing therapeutics bioavailability, and avoiding long‐term safety issues. Formulations of nano‐in‐micro dry powders for lung delivery are engineered using (S)‐ibuprofen as a model drug. These biodegradable formulations comprise nanoparticles of drug‐loaded POxylated polyurea dendrimers coated with chitosan using supercritical‐fluid‐assisted spray drying. The formulations are characterized in terms of morphology, particle‐size distribution, in vitro aerodynamic particle pulmonary distribution, and glutathione‐S‐transferase assay. It is demonstrated that ibuprofen‐loaded nanoparticles can be successfully incorporated into microspheres with adequate aerodynamic properties, mass median aerodynamic diameter (1.86–3.83 μm), and fine particle fraction (28%–45%), for deposition into the deep lung. The (S)‐ibuprofen dry powder formulations show enhanced solubility, high swelling behavior and a sustained drug release at physiologic pH. Also, POxylated polyureas decrease the (S)‐ibuprofen toxic effect on cancer cellular growth. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assays show no significant cytotoxicity on the metabolic activity of human lung adenocarcinoma ephithelial (A549) cell line for the lowest concentration (1 × 10−3 m), even for longer periods of contact with the cells (up to 120 h), and in the normal human dermal fibroblasts cell line the toxic effect is also reduced.
- 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.
- Electrodynamic tailoring of self-assembled three-dimensional electrospun constructsPublication . Reis, Tiago; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarThe rational design of three-dimensional electrospun constructs (3DECs) can lead to striking topographies and tailored shapes of electrospun materials. This new generation of materials is suppressing some of the current limitations of the usual 2D non-woven electrospun fiber mats, such as small pore sizes or only flat shaped constructs. Herein, we pursued an explanation for the self-assembly of 3DECs based on electrodynamic simulations and experimental validation. We concluded that the self-assembly process is driven by the establishment of attractive electrostatic forces between the positively charged aerial fibers and the already collected ones, which tend to acquire a negatively charged network oriented towards the nozzle. The in situ polarization degree is strengthened by higher amounts of clustered fibers, and therefore the initial high density fibrous regions are the preliminary motifs for the self-assembly mechanism. As such regions increase their in situ polarization electrostatic repulsive forces will appear, favoring a competitive growth of these self-assembled fibrous clusters. Highly polarized regions will evidence higher distances between consecutive micro-assembled fibers (MAFs). Different processing parameters – deposition time, electric field intensity, concentration of polymer solution, environmental temperature and relative humidity – were evaluated in an attempt to control material's design.
- Biocompatible oligo-oxazoline crosslinkers: Towards advanced chitosans for controlled dug releasePublication . Lopes, Mafalda; Restani, Rita; Carvalho, Marco António Paulo de; Correia, I.J.; Ricardo, Ana Aguiar; Bonifácio, VascoChitosan, a natural and abundant biopolymer has been long explored as a biocompatible material for the preparation of drug delivery devices. This strategy has been mostly accomplished using chemically crosslinked chitosan leading to more stable scaffolds. However, crosslinking has been shown to reduce both biocompatibility and swelling. In this work chitosan was crosslinked with novel biocompatible crosslinkers, based on oligo-oxazolines and glycidyl methacrylate copolymers, leading to patches with a very high swelling capacity. Dexamethasone therapeutics is strongly enhanced by a controlled release administration. This study shows that oligo-oxazoline-crosslinked chitosan is a suitable biomaterial for loading and controlled release of dexamethasone.
- Polyurea dendrimer for efficient cytosolic siRNA deliveryPublication . Restani, Rita; Conde, João; Baptista, Pedro; Cidade, Maria Teresa Varanda; Bragança, Ana; Morgado, Jorge; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana Aguiar; Bonifácio, VascoThe design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are ‘smart’ biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.
- Design of oligoaziridine-PEG coatings for efficient nanogold cellular biotaggingPublication . Silva, A. Sofia; Bonifácio, Vasco; Raje, Vivek; Branco, Paula S.; Machado, Paulo Filipe Brito; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarGold nanoparticles (AuNPs) are the most investigated nanomaterials for theragnosis applications. In a research field where live cell assays, as well as the tracking of nanomaterials into a cell's environment, are of extremely importance, water-soluble AuNPs have been intensively studied to overcome the toxic effects exerted by coatings. Unfortunately, AuNPs fluorescent tagging often fails due to self-quenching and a careful design must be carried out to maintain optoelectronic properties and biocompatibility. In this work, the synthesis of fluorescent gold nanoprobes, able to enter the cell's environment (biotags) and target the cell nucleus, was designed and the particles tracked by confocal laser scanning microscopy. The coating of AuNPs with maleimide poly(ethylene glycol) and fluorescent oligoaziridine biocompatible oligomers, resulted in robust, optically active biotags that open novel insights into cancer theragnosis.
- Natural melanin: A potential pH-responsive drug release devicePublication . Araújo, Marco; Viveiros, Raquel; Correia, Tiago R.; Correia, Ilídio Joaquim Sobreira; Bonifácio, Vasco; Casimiro, Teresa; Ricardo, Ana AguiarThis work proposes melanin as a new nanocarrier for pH-responsive drug release. Melanin is an abundant natural polymer that can be easily extracted from cuttlefish as nanoparticles with a suitable size range for drug delivery. However, despite its high potentiality, the application of this biopolymer in the pharmaceutical and biomedical fields is yet to be explored. Herein, melanin nanoparticles were impregnated with metronidazole, chosen as model antibiotic drug, using supercritical carbon dioxide. The drug release profile was investigated at acidic and physiologic pH, and the dominant mechanism was found to follow a non-Fickian transport. Drug release from melanin shows a strong pH dependency, which allied to its biocompatibility and lack of cytotoxicity envisages its potential application as nanocarrier in formulations for colon and intestine targeted drug delivery.
- 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.