2021/2022

Design and study of new drugs with possible antitumor activity – Noelia Ruiz Cuevas

8 May, 2022 por Anabel Torrente Leave a Comment

CD44 is a membrane receptor found in various types of cells in our body. This receptor binds mainly to hyaluronic acid (HA). The interaction of HA with CD44 induces changes that trigger rapid growth (proliferation) of cancer cells. Inhibition of this interaction could therefore interrupt tumour progression.
There is a specific place (small pocket) in the structure of CD44 in which small molecules could be introduced that would act as inhibitors of tumour activity. The first structures to show inhibitory activity when interacting with this pocket were molecules known as tetrahydroisoquinoline derivatives. However, it is difficult to assess the capacity of these molecules as possible antitumor agents due to their poor solubility. The main objective of this research is therefore to synthesize a series of isoquinoline salts that have good solubility in water, so facilitating the biological evaluation of these molecules.
These molecules are obtained via the reaction of isoquinoline with a chemical compound, the 3,4,5-trimethoxybenzyl group, and the introduction of different substituents in its structure, specifically in a structure known as an aromatic ring. These substitutions enable us to study the structure-activity relationship and the effect on the binding of the molecules to the aforementioned pocket in CD44.

Keywords: cancer; inhibitors; hyaluronic acid; CD44; isoquinoline.

Directed by: Olga Cruz López

Determination of serotonin using colorimetric sensors – Ricardo Rubio Rumí

7 May, 2022 por Anabel Torrente Leave a Comment

Serotonin, which is commonly known as the “happiness hormone”, is a neurotransmitter that is essential for life and is synthesized via the metabolism of tryptophan. There are various different natural ways of increasing serotonin levels, such as physical exercise, sunbathing, having a varied diet and getting sufficient sleep. An increase in the concentration of serotonin produces a state of wellbeing, relaxation, satisfaction and increases concentration and self-esteem. By contrast, serotonin deficiency can cause depression, anxiety, obsessive-compulsive disorder, etc. There is therefore a need to control its concentration in the body.

The purpose of this research is to determine serotonin in low concentrations using nanotechnology. To this end, we develop membranes with groups that react with gold nanoparticles and can perform selective serotonin retention in human plasma. The serotonin can then be determined using optical techniques (absorbance and fluorescence).

Keywords: serotonin; gold nanoparticles; colorimetric sensors.

Directed by: Antonio Luis Medina Castillo

The use of peptides to prevent binding between CD47 and SIRPα proteins in order to avoid infections – Paula Quesada Martínez

7 May, 2022 por Anabel Torrente Leave a Comment

CD47 is a protein found on the surface of the cells of infectious agents, such as viruses and bacteria. Its interaction with the signal-regulatory protein alpha (SIRPα) of the cells in our immune system induces an antiphagocytic signal, thus preventing phagocytosis, the process by which the cells in our immune system trap infectious agents and eliminate them.
Certain tumours use this mechanism to escape the action of the immune system. The same mechanism is also used by pathogens, such as the SARS-CoV-2 coronavirus or Mycobacterium tuberculosis, which induce excessive expression of CD47 to overcome our body’s defence barriers easily. Since the activation of CD47 expression is not related to the specific interaction of the pathogen with our cells, it could be used as a therapeutic target for dealing with a wide variety of infectious agents. In fact, the use of compounds with anti-CD47 activity during viral infection has been shown to promote immunity and help clear the virus more quickly.
The main objective of this work is to discover new peptides (small proteins with less than 50 amino acids), which are resistant to the enzymes that break them down (proteases) and have high affinity for either CD47 or SIRPα, so as to inhibit the interaction between them.
The activity of these peptides will then be evaluated through what is known as affinity assays. The aim of these assays is to measure the degree of affinity of the peptides with these proteins and find out more about how they bind and interact with them.

Keywords: CD47; SIRPα; peptides; infections

Directed by: Macarena Sánchez Navarro

Use of nanotechnology to transport dugs in the body – Pablo Nevado López

7 May, 2022 por Anabel Torrente Leave a Comment

Various different therapeutic strategies are applied against cancer, such as chemotherapy, radiotherapy, immunotherapy and the different combinations between them. Pharmaceutical nanotechnology is a science that has long been applied in the preparation of drug delivery vehicles. Many interesting innovations and therapeutic applications have emerged in recent years. The purpose of these systems is to protect the drug (or active ingredient), modify some of its characteristics and improve its distribution in body cells, among others.

In this study, we propose to design a new drug transport system on a nanometric scale. To this end, nanoparticles made up of two layers of polymers (chemical compounds) were designed. This multilayer is made of PLGA (poly(D,L-lactide-co-glycolide) and coated with chitosan. The nanoparticles contain an active ingredient called 5-Fluorouracil, which is classified as a cytostatic and is used to treat cancer.

Keywords: Pharmaceutical nanotechnology; cancer; drug delivery system, polymers, 5-Fluorouracil.

Work directed by: Margarita López-Viota Gallardo

Antibiotics Nanocapsulation for the treatment of caprine mastitis – Natalia López Garrido

7 May, 2022 por Anabel Torrente Leave a Comment

Goat mastitis is an important disease of the mammary gland that is commonly caused by bacterial infection. If left untreated, it constitutes a serious problema for the agri-food industry, with negative economic consequences, in terms of reduced milk production and wasted milk. Many goats suffer from chronic mastitis as a resulto f residual forms of previous mastitis, which were either not treated or were treated unsuccesfully. In these cases, the manifestations are very diverse, but, in general, abcesses and áreas of connective tissue obstructing the lactiferous ducts are found. The main objective of this Master’s tesis is to develop new antibiotic formulations, such as cefquinome, based con nanotechnology. These offer a promising alternative in the design of new, more effective therapies, which Will reduce the side effects associated with these treatments. Specifically, we intend to design and créate two types of nanoparticles (mesoporus silica and sodium hyaluronate). We will then perform a physicochemical characterization of these nanoparticles and test the encapsulation efficiency and the release profile of the proposed antibiotic.

Keywords: mastitis; goats; cefquinome; nanoparticles; mesoporus silica; sodium hyaluronate.

Directed by: Mª Encarnación Morales Hernández