Anabel Torrente

Functionalisation of frataxin with shuttle peptides to enhance its transport to the central nervous system – Beatriz Marín Diaz

1 May, 2022 por Anabel Torrente Leave a Comment

Friedreich’s Ataxia is a degenerative disease that affects one in 50,000 people. These patients have low levels of the protein frataxin, due to an inherited mutation in the gene that codes it. There is currently no cure. One of the options being studied is protein replacement therapy, which consists of administering frataxin to patients with a deficit or complete lack of this protein, so reversing the symptoms. However, in order to deliver frataxin to the central nervous system, it needs to cross the blood-brain barrier, a selective barrier that controls the transport of substances and protects the brain. Previous studies have shown that some peptides can enhance the transport of substances across the blood-brain barrier. In this study, we explored the binding of some of these peptides to the protein frataxin so as to assess whether it improved frataxin transport to the central nervous system.

Keywords: Friedreich’s ataxia; frataxin; blood-brain barrier.

Directed by: Macarena Sánchez Navarro

Cocrystals for the improvement of the physicochemical properties of the anti-inflammatory drug etenzamide – Ángel Ibáñez Gijon

30 April, 2022 por Anabel Torrente Leave a Comment

The aim of this Master’s Thesis is to obtain new multicomponent pharmaceutical solids containing the active ingredient etenzamide, which belongs to the therapeutic group of non-steroidal anti-inflammatory drugs (NSAIDs), in order to improve its solubility and therefore its oral bioavailability. For this purpose, we selected the 6 co-formers most likely to form a cocrystal with this active ingredient, namely Hydroquinone (HQ), Catechol (CAT), Resorcinol (RES), Pyrogallol (PYR), Phloroglucinol (FLU) and Orcinol (ORC). The new solids were synthesized by mechanochemical synthesis and characterised by Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Thermogravimetry (TGA). Solubility studies were conducted as were tests on stability when exposed to humidity and heat. The results obtained were very promising, since all the ethenzamide cocrystals showed an improvement in solubility compared to the active ingredient.

Keywords: multicomponent pharmaceutical solid; pharmaceutical cocrystal; etenzamide; NSAIDs; solubility

Directed by: Alicia Dominguez Martín

Evaluation of the effect of the ingestion of 3 probiotic strains and of a mixture of the three on liver damage and Akt expression in a model of non-alcoholic hepatic steatosis – Ana Isabel Álvarez Mercado

30 April, 2022 por Anabel Torrente Leave a Comment

The incidence of non-alcoholic hepatic steatosis (NASH) is increasing. This disease is characterised by the accumulation of triglycerides in the liver and can present complications ranging from non-alcoholic steatohepatitis to hepatocarcinoma. In addition, it is associated with diseases such as type 2 diabetes mellitus and obesity. NAFLD has also been linked to disorders of the gut microbiota. However, research has shown that probiotics can regenerate and regulate human gut microbiota.
The aim of this study was to evaluate the effect of three different probiotic strains – and of a mixture of the three – on several parameters of liver damage and in terms of changes in the expression of Akt, a protein involved in cell survival pathways in an animal model of NAFLD. Neutrophil accumulation was determined by assessing myeloperoxidase enzyme activity, lipid peroxidation and estimation of liver oedema. Changes in Akt protein expression were assessed after probiotic ingestion for 30 days. Probiotic intervention produced improvements in all the markers of liver damage and an increase in Akt expression.
In conclusion, the intervention with the 3 probiotic strains and with a mixture of the three tended to improve NAFLD-associated liver damage.

Keywords: non-alcoholic hepatic steatosis; probiotic; liver damage; Akt.

Directed by: Ana Isabel Álvarez Mercado