Associated Laboratory for Green Chemistry - Clean Technologies and Processes

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Publications

Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery

Publication . Silva, A. Sofia; Sousa, Ana M. L.; Cabral, Renato; Silva, Marta; Sequeira, Clarinda Costa; Miguel, Sónia; Bonifácio, Vasco; Casimiro, Teresa; Correia, I.J.; Ricardo, Ana Aguiar

Functionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2–3.8 μm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.

2017-01-19Journal article

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Ibuprofen loaded PVA/chitosan membranes: A highly efficient strategy towards an improved skin wound healing

Publication . Morgado, Patrícia I.; Miguel, Sónia P.; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana Aguiar

During 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.

2016-12-13Journal article

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Asymmetric membranes as ideal wound dressings: An overview on production methods, structure, properties and performance relationship

Publication . 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.

2015-04-25Journal article

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Nano‐in‐Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary Delivery

Publication . Restani, Rita; Silva, A. Sofia; Pires, Rita; Cabral, Renato; Correia, Ilídio Joaquim Sobreira; Casimiro, Teresa; Bonifácio, Vasco; Ricardo, Ana Aguiar

Pulmonary 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.

2016-08-03Journal article

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