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In vitro studies into establishing therapeutic bioequivalence of complex topica...

Miranda, Margarida; Volmer, Zoe; Cornick, Alicia; Goody, Aidan; Cardoso, Catarina; Pais, Alberto; Brown, Marc; Vitorino, Carla

Over the past decade, topically applied drug products have experienced extraordinary price increases, due to the shortage of multisource generic drug products. This occurrence is mainly related to the underlying challenges evolved in topical bioequivalence documentation. Although there has been continuing regulatory efforts to present surrogate in vitro methods to clinical endpoint studies, there is still a con...


Can Celecoxib Assay in Preclinical Studies Be Improved?

Mendes, Maria; Sousa, João; Pais, Alberto; Vitorino, Carla

Celecoxib, a cyclooxygenase-2 inhibitor (COX-2), is attracting considerable interest owing to its potential anticancer activity. The repurposing strategy of this drug, however, requires preclinical assessment involving the use of increasingly improved analytical methods. In this work, a rapid, accurate, precise, and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed f...


Reactivity of ethyl nitrosoacrylate toward pyrrole, indole and pyrrolo[3,2-c]ca...

Benzi, Alice; Lopes, Susana M. M.; Nunes, Sandra; Giorgi, Gianluca; Bianchi, Lara; Tavani, Cinzia; Pais, Alberto; Petrillo, Giovanni

Nitrosoalkenes react with 8-methyl-1,6-dihydropyrrolo[3,2-c]carbazole to give both 2- and 3-alkylated products via hetero-Diels-Alder reaction followed by the cycloadduct ring-opening. Quantum chemical calculations, at DFT level of theory, were carried out to investigate the regioselectivity of the cycloaddition of ethyl nitrosoacrylate with 1,6-dihydropyrrolo[3,2-c]carbazoles as well as with pyrrole and indole...


A two-pronged approach against glioblastoma: drug repurposing and nanoformulati...

Mendes, Maria; Branco, Francisco; Vitorino, Rui; Sousa, João; Pais, Alberto; Vitorino, Carla

Glioblastoma (GB) is one of the most lethal types of neoplasms. Its biologically aggressive nature and the presence of the blood-brain barrier (BBB) limit the efficacy of standard therapies. Several strategies are currently being developed to both overcome the BBB and deliver drugs site specifically to tumor cells. This work hypothesizes a two-pronged approach to tackle GB: drug repurposing with celecoxib (CXB)...


A Stepwise Framework for the Systematic Development of Lipid Nanoparticles

Basso, João; Mendes, Maria; Cova, Tânia; Sousa, João; Pais, Alberto; Fortuna, Ana; Vitorino, Rui; Vitorino, Carla

A properly designed nanosystem aims to deliver an optimized concentration of the active pharmaceutical ingredient (API) at the site of action, resulting in a therapeutic response with reduced adverse effects. Due to the vast availability of lipids and surfactants, producing stable lipid dispersions is a double-edged sword: on the one hand, the versatility of composition allows for a refined design and tuning of...


New Advances in Biomedical Application of Polymeric Micelles

Figueiras, Ana; Domingues, Cátia; Jarak, Ivana; Santos, Ana Isabel; Parra, Ana; Pais, Alberto; Alvarez-Lorenzo, Carmen; Concheiro, Angel

Abstract In the last decade, nanomedicine has arisen as an emergent area of medicine, which studies nanometric systems, namely polymeric micelles (PMs), that increase the solubility and the stability of the encapsulated drugs. Furthermore, their application in dermal drug delivery is also relevant. PMs present unique characteristics because of their unique core-shell architecture. They are colloidal dispersions...


Poly(β-cyclodextrin)-Activated Carbon Gel Composites for Removal of Pesticides ...

Utzeri, Gianluca; Veríssimo, Luís; Murtinho, Dina; Pais, Alberto; Perrin, F. Xavier; Ziarelli, Fabio; Iordache, Tanta-Verona; Sarbu, Andrei

Pesticides are widely used in agriculture to increase and protect crop production. A substantial percentage of the active substances applied is retained in the soil or flows into water courses, constituting a very relevant environmental problem. There are several methods for the removal of pesticides from soils and water; however, their efficiency is still a challenge. An alternative to current methods relies o...


Transport and photophysical studies on porphyrin-containing sulfonated poly(eth...

Sousa, Joana F. M.; Pina, João; Gomes, Carla; Dias, Lucas D.; Pereira, Mariette M.; Murtinho, Dina; Dias, Paula; Azevedo, João; Mendes, Adélio

The development of efficient and reliable membranes for redox flow batteries (RFBs) with high ionic conductivity and selectivity is challenging. Aiming the development of better membranes, we have synthesized porphyrin-containing sulfonated poly(etheretherketone) (SPEEK). In particular, the effect of water soluble 5,10,15,20-tetrakis(N-methyl-4-pyridinyl)porphyrin iodide (TMePyPI4) and its Cu(II) complex, 5,10,...


Expediting Disulfiram Assays through a Systematic Analytical Quality by Design ...

Basso, João; Ramos, Maria Luísa; Pais, Alberto; Vitorino, Rui; Fortuna, Ana; Vitorino, Carla

An Analytical Quality by Design (AQbD) approach is presented, aiming at the development and validation of an HPLC method for the quantification of disulfiram and copper diethyldithiocarbamate in lipid nanoparticles. Following the definition of the analytical target profile (ATP), encompassing the critical analytical attributes (CAA), a two-level risk assessment strategy (Ishikawa diagram—failure mode and effect...


Poly(β-cyclodextrin)-Activated Carbon Gel Composites for Removal of Pesticides ...

Utzeri, Gianluca; Veríssimo, Luís; Murtinho, Dina; Pais, Alberto; Perrin, F. Xavier; Ziarelli, Fabio; Iordache, Tanta-Verona; Sarbu, Andrei

Pesticides are widely used in agriculture to increase and protect crop production. A substantial percentage of the active substances applied is retained in the soil or flows into water courses, constituting a very relevant environmental problem. There are several methods for the removal of pesticides from soils and water; however, their efficiency is still a challenge. An alternative to current methods relies o...


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