Loading...
4 results
Search Results
Now showing 1 - 4 of 4
- 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.
- Novel Methodology Based on Biomimetic Superhydrophobic Substrates to Immobilize Cells and Proteins in Hydrogel Spheres for Applications in Bone RegenerationPublication . Lima, Ana; Batista, Patrícia Sofia Pinhanços; Valente, Tiago António Martins; Silva, A. Sofia; Correia, Ilídio Joaquim Sobreira; Mano, JoãoCell-based therapies for regenerative medicine have been characterized by the low retention and integration of injected cells into host structures. Cell immobilization in hydrogels for target cell delivery has been developed to circumvent this issue. In this work mesenchymal stem cells isolated from Wistar rats bone marrow (rMSCs) were immobilized in alginate beads fabricated using an innovative approach involving the gellification of the liquid precursor droplets onto biomimetic superhydrophobic surfaces without the need of any precipitation bath. The process occurred in mild conditions preventing the loss of cell viability. Furthermore, fibronectin (FN) was also immobilized inside alginate beads with high efficiency in order to mimic the composition of the extracellular matrix. This process occurred in a very fast way (around 5 min), at room temperature, without aggressive mechanical strengths or particle aggregation. The methodology employed allowed the production of alginate beads exhibiting a homogenous rMSCs and FN distribution. Encapsulated rMSCs remained viable and were released from the alginate for more than 20 days. In vivo assays were also performed, by implanting these particles in a calvarial bone defect to evaluate their potential for bone tissue regeneration. Microcomputed tomography and histological analysis results showed that this hybrid system accelerated bone regeneration process. The methodology employed had a dual role by preventing cell and FN loss and avoiding any contamination of the beads or exchange of molecules with the surrounding environment. In principle, the method used for cell encapsulation could be extended to other systems aimed to be used in tissue regeneration strategies.
- 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.
- Nanogold POxylation: towards always-on fluorescent lung cancer targetingPublication . Silva, A. Sofia; Silva, Marta; Miguel, Sónia P.; Bonifácio, Vasco; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarGold nanoparticles (GNPs) are one of most investigated nanomaterials for lung cancer diagnosis and therapy (theragnosis). For imaging purposes, GNPs are often tagged with fluorescent probes, but unfortunately the associated plasmon resonance effect leads to fluorescence self-quenching, thus precluding accurate localization. In this study, biocompatible GNPs targeted with a laminin fragment were successfully engineered using fluorescent oligo-oxazolines produced in supercritical carbon dioxide. The architecture and properties of the POxylated constructs were fully characterized and confocal laser scanning microscopy measurements demonstrated a higher cellular uptake into A549 lung cancer cells through an active targeting mechanism.