Development of nanoparticulate systems for the administration of antitumor agents using Artificial Intelligence tools.
Authorship
A.A.L.
Master in Drug Research and Development
A.A.L.
Master in Drug Research and Development
Defense date
07.15.2024 09:20
07.15.2024 09:20
Summary
With the purpose of obtaining more effective and personalized treatments, the pharmaceutical industry continues to focus on the development of new drugs that combine different areas of knowledge such as cellular and molecular biology, materials sciences, pharmaceutical sciences and medicine. Nanotechnology bursts into this context, offering the possibility of developing advanced drug delivery systems. Nanoparticulate systems are a multifunctional technology due to their design that allows the incorporation of different therapeutic modalities, and the possibility of being used in the same way in the diagnosis and monitoring of the response to medical treatments. For the manufacture of the nanostructured lipid carriers NLCs, Compritol 888 ATO and Transcutol P were selected as lipid components, due to the high solubility of the drug B Lapachona in them, and Tween80 and lecithin as surfactants. The combination of ANN Artificial Neural Networks and fuzzy logic systems was used to obtain NFL neurofuzzy logic that allows for simple information on large data sets in the form of written language. The objective of this work is to explore the design space of NLC, as carriers of the antitumor B Lapachona. The aim is to model the effects of the variables involved in the NLC production process on the characteristics of the systems, to know the possibilities of encapsulating this drug and, ultimately, to find the most appropriate combination to obtain NLCs with homogeneous distributions. Despite the variability in the results produced by the NLCs formulated in each variable studied, they allowed us to validate the applicability of the NFL in the design of NLCs loaded with B Lapachona.
With the purpose of obtaining more effective and personalized treatments, the pharmaceutical industry continues to focus on the development of new drugs that combine different areas of knowledge such as cellular and molecular biology, materials sciences, pharmaceutical sciences and medicine. Nanotechnology bursts into this context, offering the possibility of developing advanced drug delivery systems. Nanoparticulate systems are a multifunctional technology due to their design that allows the incorporation of different therapeutic modalities, and the possibility of being used in the same way in the diagnosis and monitoring of the response to medical treatments. For the manufacture of the nanostructured lipid carriers NLCs, Compritol 888 ATO and Transcutol P were selected as lipid components, due to the high solubility of the drug B Lapachona in them, and Tween80 and lecithin as surfactants. The combination of ANN Artificial Neural Networks and fuzzy logic systems was used to obtain NFL neurofuzzy logic that allows for simple information on large data sets in the form of written language. The objective of this work is to explore the design space of NLC, as carriers of the antitumor B Lapachona. The aim is to model the effects of the variables involved in the NLC production process on the characteristics of the systems, to know the possibilities of encapsulating this drug and, ultimately, to find the most appropriate combination to obtain NLCs with homogeneous distributions. Despite the variability in the results produced by the NLCs formulated in each variable studied, they allowed us to validate the applicability of the NFL in the design of NLCs loaded with B Lapachona.
Direction
LANDIN PEREZ, MARIANA (Tutorships)
ROUCO TABOADA, HELENA (Co-tutorships)
LANDIN PEREZ, MARIANA (Tutorships)
ROUCO TABOADA, HELENA (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Peptide-based hydrogels with self-assembly capacity for drug release
Authorship
L.G.M.
Master in Drug Research and Development
L.G.M.
Master in Drug Research and Development
Defense date
07.15.2024 10:00
07.15.2024 10:00
Summary
Peptide-based hydrogels have a great interest in the area of controlled for drug delivery. Specifically, ultrashort and amphiphilic, due to their versatility and biocompatibility. These peptides have the ability to self-assemble and co-assemble, resulting in hydrogels with nano-fibrillar structures. This work focuses on obtaining hydrogels based on two self-assembly peptides: an ultrashort peptide, Fmoc-FF and an amphiphilic peptide, E3. These peptides were combined with collagen to create drug delivery systems for antibacterial agents useful in treating skin infections. The co-assembly between both components was confirmed using techniques such as DLS, which quantifies changes in aggregate size, and FTIR, which studies the secondary structure of the proteins present in the hydrogels. The obtained hydrogels were also characterized in terms of cytocompatibility, collagen incorporation and their ability to modulate the release of the antibiotic vancomycin. The results showed that both hydrogel formulations efficiently incorporate collagen and can modulate the release of vancomycin, with E3/Collagen hydrogels providing more sustained release. Regarding cytocompatibility, the introduction of collagen contributes to increased cell viability in cells treated with the hydrogels, with the best results observed in the E3/collagen formulations. Finally, antibacterial activity studies demonstrated the effectiveness of Fmoc-FF/Collagen gels loaded with vancomycin against Staphylococcus aureus. These results indicate the possible usefulness of the systems for the treatment of infections caused by said pathogen.
Peptide-based hydrogels have a great interest in the area of controlled for drug delivery. Specifically, ultrashort and amphiphilic, due to their versatility and biocompatibility. These peptides have the ability to self-assemble and co-assemble, resulting in hydrogels with nano-fibrillar structures. This work focuses on obtaining hydrogels based on two self-assembly peptides: an ultrashort peptide, Fmoc-FF and an amphiphilic peptide, E3. These peptides were combined with collagen to create drug delivery systems for antibacterial agents useful in treating skin infections. The co-assembly between both components was confirmed using techniques such as DLS, which quantifies changes in aggregate size, and FTIR, which studies the secondary structure of the proteins present in the hydrogels. The obtained hydrogels were also characterized in terms of cytocompatibility, collagen incorporation and their ability to modulate the release of the antibiotic vancomycin. The results showed that both hydrogel formulations efficiently incorporate collagen and can modulate the release of vancomycin, with E3/Collagen hydrogels providing more sustained release. Regarding cytocompatibility, the introduction of collagen contributes to increased cell viability in cells treated with the hydrogels, with the best results observed in the E3/collagen formulations. Finally, antibacterial activity studies demonstrated the effectiveness of Fmoc-FF/Collagen gels loaded with vancomycin against Staphylococcus aureus. These results indicate the possible usefulness of the systems for the treatment of infections caused by said pathogen.
Direction
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
ROUCO TABOADA, HELENA (Co-tutorships)
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
ROUCO TABOADA, HELENA (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Functional characterization of gpvi collagen receptor inhibitory molecules in platelets
Authorship
M.D.F.
Master in Drug Research and Development
M.D.F.
Master in Drug Research and Development
Defense date
07.15.2024 09:40
07.15.2024 09:40
Summary
Cardiovascular diseases are currently the leading cause of death worldwide, causing the loss of 17.3 million lives per year. Platelets are directly involved in their development; anucleated cells that participate in thrombus formation to maintain vascular hemostasis, but which in pathological circumstances can obstruct blood vessels. Because antithrombotic therapy for their prevention and treatment has high bleeding risks, research is needed into new antiplatelet drugs that target different platelet receptors, such as the collagen receptor Glycoprotein VI (GPVI). New drugs could prevent and treat pathological thrombus formation more precisely without increasing the risk of bleeding, improving the safety and efficacy of antithrombotic therapy and the management of severe cardiovascular disease in the clinic. In this work we characterize the inhibitory activity of the molecules SEDN2-22 and SEDN2-28, synthetic structural derivatives of SEDN2, a molecule previously identified by our research group with the capacity to selectively inhibit GPVI. Characterization will be by platelet aggregation and spreading studies and western blot. The results show that both molecules are able to selectively inhibit GPVI-mediated platelet activation. The results obtained in this work are a step towards the identification of a new compound with optimal pharmacological properties capable of blocking GPVI-mediated platelet activation and minimizing the problems of current antithrombotic therapy.
Cardiovascular diseases are currently the leading cause of death worldwide, causing the loss of 17.3 million lives per year. Platelets are directly involved in their development; anucleated cells that participate in thrombus formation to maintain vascular hemostasis, but which in pathological circumstances can obstruct blood vessels. Because antithrombotic therapy for their prevention and treatment has high bleeding risks, research is needed into new antiplatelet drugs that target different platelet receptors, such as the collagen receptor Glycoprotein VI (GPVI). New drugs could prevent and treat pathological thrombus formation more precisely without increasing the risk of bleeding, improving the safety and efficacy of antithrombotic therapy and the management of severe cardiovascular disease in the clinic. In this work we characterize the inhibitory activity of the molecules SEDN2-22 and SEDN2-28, synthetic structural derivatives of SEDN2, a molecule previously identified by our research group with the capacity to selectively inhibit GPVI. Characterization will be by platelet aggregation and spreading studies and western blot. The results show that both molecules are able to selectively inhibit GPVI-mediated platelet activation. The results obtained in this work are a step towards the identification of a new compound with optimal pharmacological properties capable of blocking GPVI-mediated platelet activation and minimizing the problems of current antithrombotic therapy.
Direction
GARCIA ALONSO, ANGEL (Tutorships)
GARCIA ALONSO, ANGEL (Tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Development of Artificial Breast Cancer Tumour Models for Evaluating Anti-Tumour Drug Efficacy
Authorship
U.G.D.
Master in Drug Research and Development
U.G.D.
Master in Drug Research and Development
Defense date
07.15.2024 10:20
07.15.2024 10:20
Summary
The role that the extracellular matrix (ECM) plays in the development of breast tumours and drug resistance motivates the creation of 3D models capable of replicating its characteristics. In this study, we fabricated core-shell hydrogel beads from pre-gels of alginate, gelatin, and collagen I (Col1) by extrusion through a coaxial needle. Breast cancer cells (BCCs) can proliferate on all prototypes designed, forming spheroids and cell aggregates. Addition of Col1 to the hydrogels increases malignancy markers expression (Col1A1, HAS2, LAMB1, CDH1, YAP1, and WWTR1) in MCF-7 cells and enhances invadopodia formation (HIF1a, WASL, and BACT). Furthermore, hydrogels designed showed higher doxorubicin resistance, making them good candidates as breast cancer models for chemotherapeutic agents and drug screening.
The role that the extracellular matrix (ECM) plays in the development of breast tumours and drug resistance motivates the creation of 3D models capable of replicating its characteristics. In this study, we fabricated core-shell hydrogel beads from pre-gels of alginate, gelatin, and collagen I (Col1) by extrusion through a coaxial needle. Breast cancer cells (BCCs) can proliferate on all prototypes designed, forming spheroids and cell aggregates. Addition of Col1 to the hydrogels increases malignancy markers expression (Col1A1, HAS2, LAMB1, CDH1, YAP1, and WWTR1) in MCF-7 cells and enhances invadopodia formation (HIF1a, WASL, and BACT). Furthermore, hydrogels designed showed higher doxorubicin resistance, making them good candidates as breast cancer models for chemotherapeutic agents and drug screening.
Direction
ALVAREZ LORENZO, CARMEN ISABEL (Tutorships)
BLANCO FERNANDEZ, BARBARA (Co-tutorships)
ALVAREZ LORENZO, CARMEN ISABEL (Tutorships)
BLANCO FERNANDEZ, BARBARA (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Fast manufacturing of personalized medications using a pharmaceutical 3D printer
Authorship
D.G.G.
Master in Drug Research and Development
D.G.G.
Master in Drug Research and Development
Defense date
07.15.2024 10:40
07.15.2024 10:40
Summary
In recent decades, personalized medicine has aimed to individualize pharmacological treatments considering factors such as age, sex, and patients' health conditions. 3D printing has emerged as an innovative tool for manufacturing personalized medications, adjusting doses, forms, and release profiles. This study focuses on semi-solid extrusion (SSE) technology and mold filling (MF) technique to create melatonin and cannabidiol (CBD) troches. Pharmaceutical inks based on polyethylene glycol (PEG 1450) and others with a commercial base (Techna 20SF) were developed. These pharmaceutical inks were processed in a pharmaceutical 3D printer to fill molds and produce troches of various doses, including bi-layer combinations of melatonin and CBD. Friability, thermal behavior, drug content uniformity, and dissolution profile of the produced troches were evaluated. Results indicated that the troches exhibited adequate mechanical properties during handling. Thermal analysis, supported by drug content uniformity results, confirmed the stability of active ingredients in formulations at working temperature. Drug dosage was uniform for melatonin formulations, while for CBD, it exceeded the limits set by the European Pharmacopoeia. Dissolution profiles showed immediate drug release, meeting therapeutic requirements. In conclusion, the MF technique combined with pharmaceutical 3D printers and customized inks enables rapid and automated production of troches with precise dosages and improved organoleptic characteristics, effectively contributing to personalized medicine and adherence to pharmacological treatments.
In recent decades, personalized medicine has aimed to individualize pharmacological treatments considering factors such as age, sex, and patients' health conditions. 3D printing has emerged as an innovative tool for manufacturing personalized medications, adjusting doses, forms, and release profiles. This study focuses on semi-solid extrusion (SSE) technology and mold filling (MF) technique to create melatonin and cannabidiol (CBD) troches. Pharmaceutical inks based on polyethylene glycol (PEG 1450) and others with a commercial base (Techna 20SF) were developed. These pharmaceutical inks were processed in a pharmaceutical 3D printer to fill molds and produce troches of various doses, including bi-layer combinations of melatonin and CBD. Friability, thermal behavior, drug content uniformity, and dissolution profile of the produced troches were evaluated. Results indicated that the troches exhibited adequate mechanical properties during handling. Thermal analysis, supported by drug content uniformity results, confirmed the stability of active ingredients in formulations at working temperature. Drug dosage was uniform for melatonin formulations, while for CBD, it exceeded the limits set by the European Pharmacopoeia. Dissolution profiles showed immediate drug release, meeting therapeutic requirements. In conclusion, the MF technique combined with pharmaceutical 3D printers and customized inks enables rapid and automated production of troches with precise dosages and improved organoleptic characteristics, effectively contributing to personalized medicine and adherence to pharmacological treatments.
Direction
GOYANES GOYANES, ALVARO (Tutorships)
GOYANES GOYANES, ALVARO (Tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
3D printing of polypills by direct powder extrusion to increase drug dissolution rate
Authorship
V.H.
Master in Drug Research and Development
V.H.
Master in Drug Research and Development
Defense date
07.15.2024 11:20
07.15.2024 11:20
Summary
The low solubility of many drugs, especially those classified as class II and IV according to the Biopharmaceutics Classification System (BCS), poses significant challenges in the pharmaceutical industry due to its association with low bioavailability. Ramipril and indapamide, both class II with low solubility, exemplify the need for advanced strategies to enhance their therapeutic efficacy. Although methods such as micronization, salt formation, and cyclodextrin complexation have been investigated to increase solubility, they often present efficacy issues and high costs. This study developed pharmaceutical inks containing ramipril and indapamide, printed using a pharmaceutical 3D printer employing direct powder extrusion (DPE) to produce polypills. During printing, amorphous solid dispersions (ASD) of the drugs were formed at low temperatures to preserve stability, overcoming a key limitation of this technique. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses confirmed amorphization, improving solubility. In vitro dissolution tests demonstrated a significantly rapid and uniform release, with 75% of the drugs released within 45 minutes. This work demonstrates for the first time the potential of 3D DPE printing for immediate-release polypills of ramipril and indapamide. This could enhance treatments for polymedicated patients by simplifying administration and increasing adherence. Furthermore, dose customization with DPE could specifically benefit patients with conditions such as hypertension, reducing the risk of adverse reactions.
The low solubility of many drugs, especially those classified as class II and IV according to the Biopharmaceutics Classification System (BCS), poses significant challenges in the pharmaceutical industry due to its association with low bioavailability. Ramipril and indapamide, both class II with low solubility, exemplify the need for advanced strategies to enhance their therapeutic efficacy. Although methods such as micronization, salt formation, and cyclodextrin complexation have been investigated to increase solubility, they often present efficacy issues and high costs. This study developed pharmaceutical inks containing ramipril and indapamide, printed using a pharmaceutical 3D printer employing direct powder extrusion (DPE) to produce polypills. During printing, amorphous solid dispersions (ASD) of the drugs were formed at low temperatures to preserve stability, overcoming a key limitation of this technique. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses confirmed amorphization, improving solubility. In vitro dissolution tests demonstrated a significantly rapid and uniform release, with 75% of the drugs released within 45 minutes. This work demonstrates for the first time the potential of 3D DPE printing for immediate-release polypills of ramipril and indapamide. This could enhance treatments for polymedicated patients by simplifying administration and increasing adherence. Furthermore, dose customization with DPE could specifically benefit patients with conditions such as hypertension, reducing the risk of adverse reactions.
Direction
GOYANES GOYANES, ALVARO (Tutorships)
GOYANES GOYANES, ALVARO (Tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Development of nanosystems for application in progressive bone heteroplasia disease.
Authorship
M.E.J.R.
Master in Drug Research and Development
M.E.J.R.
Master in Drug Research and Development
Defense date
07.15.2024 11:40
07.15.2024 11:40
Summary
Progressive bone heteroplasia is a very unusual genetic bone disease that is clinically described by the progressive formation of extraskeletal bone, damaging subcutaneous and muscular tissue. This disorder is caused by mutations in the GNAS gene, which encodes a G protein that plays a key role in different cell signaling pathways that control bone development. Deficiency of this functional protein leads to dysregulation in the differentiation of mesenchymal stem cells inducing excessive osteoinduction. At present there is no curative or palliative treatment for this pathology, so developing new forms of treatment is essential to find a solution to this problem. This project aims to design hybrid fusogenic nanoparticles loaded with a protein for supplementation with protein G. In this way, the intracellular release of this protein would be able to reverse or slow the progression of the disease. For this purpose, nanoparticles loaded with a model protein, similar in size to the problem protein causing the disease, were developed and characterized in order to incubate them in cells and characterize their internalization by microscopy. The results showed a correct internalization of the nanoparticles without producing cytotoxicity, so this study could serve as a proof of concept for a therapeutic strategy to treat progressive bone heteroplasia.
Progressive bone heteroplasia is a very unusual genetic bone disease that is clinically described by the progressive formation of extraskeletal bone, damaging subcutaneous and muscular tissue. This disorder is caused by mutations in the GNAS gene, which encodes a G protein that plays a key role in different cell signaling pathways that control bone development. Deficiency of this functional protein leads to dysregulation in the differentiation of mesenchymal stem cells inducing excessive osteoinduction. At present there is no curative or palliative treatment for this pathology, so developing new forms of treatment is essential to find a solution to this problem. This project aims to design hybrid fusogenic nanoparticles loaded with a protein for supplementation with protein G. In this way, the intracellular release of this protein would be able to reverse or slow the progression of the disease. For this purpose, nanoparticles loaded with a model protein, similar in size to the problem protein causing the disease, were developed and characterized in order to incubate them in cells and characterize their internalization by microscopy. The results showed a correct internalization of the nanoparticles without producing cytotoxicity, so this study could serve as a proof of concept for a therapeutic strategy to treat progressive bone heteroplasia.
Direction
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
Gómez Vaamonde, Rodolfo (Co-tutorships)
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
Gómez Vaamonde, Rodolfo (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Microparticles with senolytic drugs for the treatment of osteoarthritis
Authorship
A.A.L.L.
Master in Drug Research and Development
A.A.L.L.
Master in Drug Research and Development
Defense date
07.15.2024 12:00
07.15.2024 12:00
Summary
Osteoarthritis (OA) is a degenerative disease of the articular cartilage that leads to pain, inflammation, and immobility. Currently, treatment focuses on symptom relief through anti-inflammatory therapy without addressing the underlying causes of the condition. Recent evidence suggests that cellular senescence of chondrocytes, which halts the cell cycle and releases destructive cytokines, may be a key factor in OA. Fenofibrate, a drug used for treating dyslipidemia, has been found to reduce the viability of senescent chondrocytes and improve cartilage degradation in in vivo studies. However, its low bioavailability and rapid joint clearance limit its effectiveness. This study proposes the synthesis of PLGA polymeric microparticles for the sustained release of fenofibrate in the joint. Two PLGA formulations with different combinations of lactic and glycolic acids and molecular weights were prepared and effectively encapsulated fenofibrate. These formulations exhibited physicochemical properties compatible with intra-articular administration. Additionally, the impact of gamma radiation sterilization on these formulations was assessed, revealing changes in matrix structure and drug release rate. Finally, in vitro studies with human chondrocytes confirmed that the microparticles preserved the pharmacological activity observed with free drug, demonstrating their therapeutic potential for OA.
Osteoarthritis (OA) is a degenerative disease of the articular cartilage that leads to pain, inflammation, and immobility. Currently, treatment focuses on symptom relief through anti-inflammatory therapy without addressing the underlying causes of the condition. Recent evidence suggests that cellular senescence of chondrocytes, which halts the cell cycle and releases destructive cytokines, may be a key factor in OA. Fenofibrate, a drug used for treating dyslipidemia, has been found to reduce the viability of senescent chondrocytes and improve cartilage degradation in in vivo studies. However, its low bioavailability and rapid joint clearance limit its effectiveness. This study proposes the synthesis of PLGA polymeric microparticles for the sustained release of fenofibrate in the joint. Two PLGA formulations with different combinations of lactic and glycolic acids and molecular weights were prepared and effectively encapsulated fenofibrate. These formulations exhibited physicochemical properties compatible with intra-articular administration. Additionally, the impact of gamma radiation sterilization on these formulations was assessed, revealing changes in matrix structure and drug release rate. Finally, in vitro studies with human chondrocytes confirmed that the microparticles preserved the pharmacological activity observed with free drug, demonstrating their therapeutic potential for OA.
Direction
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Nanostructured Lipid Systems of Cannabigerol for the Treatment of Psoriasis
Authorship
M.O.G.
Master in Drug Research and Development
M.O.G.
Master in Drug Research and Development
Defense date
07.15.2024 12:20
07.15.2024 12:20
Summary
Cannabigerol (CBG), a phytocannabinoid, has potential therapeutic properties for the treatment of psoriasis due to its ability to reduce pro-inflammatory cytokines and chemokines involved in the pathogenesis of this disease. The purpose of this study was to develop and characterize CBG-loaded nanostructured lipid systems (SLNs) for the topical treatment of psoriasis. The SLNs, as innovative lipid nanosystems, were designed to enhance the penetration and accumulation of CBG into the skin. During the study, SLN-SBGs were structurally and physicochemically characterized, including particle size, polydispersity index (PDI), zeta potential (PZ), stability, and encapsulation efficiency (EE) of CBG. In vitro release studies were conducted to understand the release behavior of CBG from SLNs, in addition to evaluating the skin permeability and retention of CBG in skin. In vitro and in vivo studies were also conducted to evaluate its safety and toxicity. The results showed a size of 179,7 nm, a PDI of 0,20 and a PZ of negative. The SLNs were stable, with a high EE (up to 99%). The in vitro release study conformed to the Peppas-Korsmeyer model with R2 = 0.9734. SLN-CBG proved efficacy to penetrate to deep skin layers and safety in cell viability and acute toxicity studies.The incorporation of SLN-CBG into hydrogels showed a CBG release profile that underlines its potential for the treatment of dermatological diseases such as psoriasis.
Cannabigerol (CBG), a phytocannabinoid, has potential therapeutic properties for the treatment of psoriasis due to its ability to reduce pro-inflammatory cytokines and chemokines involved in the pathogenesis of this disease. The purpose of this study was to develop and characterize CBG-loaded nanostructured lipid systems (SLNs) for the topical treatment of psoriasis. The SLNs, as innovative lipid nanosystems, were designed to enhance the penetration and accumulation of CBG into the skin. During the study, SLN-SBGs were structurally and physicochemically characterized, including particle size, polydispersity index (PDI), zeta potential (PZ), stability, and encapsulation efficiency (EE) of CBG. In vitro release studies were conducted to understand the release behavior of CBG from SLNs, in addition to evaluating the skin permeability and retention of CBG in skin. In vitro and in vivo studies were also conducted to evaluate its safety and toxicity. The results showed a size of 179,7 nm, a PDI of 0,20 and a PZ of negative. The SLNs were stable, with a high EE (up to 99%). The in vitro release study conformed to the Peppas-Korsmeyer model with R2 = 0.9734. SLN-CBG proved efficacy to penetrate to deep skin layers and safety in cell viability and acute toxicity studies.The incorporation of SLN-CBG into hydrogels showed a CBG release profile that underlines its potential for the treatment of dermatological diseases such as psoriasis.
Direction
OTERO ESPINAR, FRANCISCO JAVIER (Tutorships)
DIAZ TOME, VICTORIA (Co-tutorships)
OTERO ESPINAR, FRANCISCO JAVIER (Tutorships)
DIAZ TOME, VICTORIA (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Supramolecular nanofibers as next-generation antimicrobials
Authorship
A.R.R.
Master in Drug Research and Development
A.R.R.
Master in Drug Research and Development
Defense date
07.15.2024 12:40
07.15.2024 12:40
Summary
Antimicrobial resistance has become a global threat to public health, with an increasing impact on morbidity and mortality. The biomolecular mechanisms of antibiotic resistance are diverse and complex, making it difficult to develop effective new drugs that overcome these barriers. Antimicrobial peptides (AMPs) are a promising alternative to traditional antibiotics that present a mechanism of action without a specific target, which reduces the likelihood of resistance development. However, the clinical application of AMPs is limited by their poor stability in biological media and high toxicity. In this work, we propose the development of self assembling AMPs as a new strategy to combat antimicrobial resistance. These AMPs would be composed of inactive peptides that self assemble into supramolecular nanofibers with antimicrobial activity. This strategy presents several advantages over conventional AMPs, including higher stability and lower toxicity. The main objective of this work is to synthesize and evaluate preliminarily peptide sequences with self assembly potential and antimicrobial effect. Peptides based on beta amyloid peptide sequences will be synthesized and their antimicrobial activity and cytocompatibility will be evaluated. This work has the potential to contribute to the development of new, more effective and safer AMPs to combat antimicrobial resistance.
Antimicrobial resistance has become a global threat to public health, with an increasing impact on morbidity and mortality. The biomolecular mechanisms of antibiotic resistance are diverse and complex, making it difficult to develop effective new drugs that overcome these barriers. Antimicrobial peptides (AMPs) are a promising alternative to traditional antibiotics that present a mechanism of action without a specific target, which reduces the likelihood of resistance development. However, the clinical application of AMPs is limited by their poor stability in biological media and high toxicity. In this work, we propose the development of self assembling AMPs as a new strategy to combat antimicrobial resistance. These AMPs would be composed of inactive peptides that self assemble into supramolecular nanofibers with antimicrobial activity. This strategy presents several advantages over conventional AMPs, including higher stability and lower toxicity. The main objective of this work is to synthesize and evaluate preliminarily peptide sequences with self assembly potential and antimicrobial effect. Peptides based on beta amyloid peptide sequences will be synthesized and their antimicrobial activity and cytocompatibility will be evaluated. This work has the potential to contribute to the development of new, more effective and safer AMPs to combat antimicrobial resistance.
Direction
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
INSUA LOPEZ, IGNACIO (Co-tutorships)
DIAZ RODRIGUEZ, PATRICIA (Tutorships)
INSUA LOPEZ, IGNACIO (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Early Molecular Nanodiagnostics of Brain Tumors using Immuno-PET
Authorship
J.R.O.
Master in Drug Research and Development
J.R.O.
Master in Drug Research and Development
Defense date
07.15.2024 13:00
07.15.2024 13:00
Summary
Glioblastoma (GBM) is the most common and destructive brain tumor, with a median survival of 12-15 months. Current therapeutic approaches, including surgery followed by chemotherapy and radiation, are often ineffective due to the challenge of crossing the blood-brain barrier (BBB), which prevents over 98% of chemotherapeutic drugs from reaching the brain. This barrier not only complicates treatment but also hampers early-stage diagnosis of GBM. Recently, Immuno-PET has emerged as a promising non-invasive, whole-body imaging tool. It focuses on the tumor selectivity of monoclonal antibodies (mAbs) by directly measuring in vivo target expression in tumor tissue. This study focuses on the rational design of two promising nanoemulsions (NEs) as nanocarriers capable of crossing the BBB and target glioma cells. This NEs would also be radiolabeled to achieve an early-stage diagnosis of GBM by Immuno-PET. We evaluated their physicochemical properties, stability, and radiolabeling efficiency. The results indicate that the designed NEs show promise as vehicles for targeted delivery of diagnostic and therapeutic agents in GBM. These findings pave the way for further exploration of nanocarrier-based strategies combined with advanced imaging techniques like PET, for efficient GBM theragnostic.
Glioblastoma (GBM) is the most common and destructive brain tumor, with a median survival of 12-15 months. Current therapeutic approaches, including surgery followed by chemotherapy and radiation, are often ineffective due to the challenge of crossing the blood-brain barrier (BBB), which prevents over 98% of chemotherapeutic drugs from reaching the brain. This barrier not only complicates treatment but also hampers early-stage diagnosis of GBM. Recently, Immuno-PET has emerged as a promising non-invasive, whole-body imaging tool. It focuses on the tumor selectivity of monoclonal antibodies (mAbs) by directly measuring in vivo target expression in tumor tissue. This study focuses on the rational design of two promising nanoemulsions (NEs) as nanocarriers capable of crossing the BBB and target glioma cells. This NEs would also be radiolabeled to achieve an early-stage diagnosis of GBM by Immuno-PET. We evaluated their physicochemical properties, stability, and radiolabeling efficiency. The results indicate that the designed NEs show promise as vehicles for targeted delivery of diagnostic and therapeutic agents in GBM. These findings pave the way for further exploration of nanocarrier-based strategies combined with advanced imaging techniques like PET, for efficient GBM theragnostic.
Direction
ALONSO FERNANDEZ, MARIA JOSEFA (Tutorships)
Aguiar Fernández, Pablo (Co-tutorships)
ALONSO FERNANDEZ, MARIA JOSEFA (Tutorships)
Aguiar Fernández, Pablo (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Curcumin-Loaded Methylcellulose Aerogels for Wound Treatment
Authorship
C.A.S.F.
Master in Drug Research and Development
C.A.S.F.
Master in Drug Research and Development
Defense date
07.15.2024 13:20
07.15.2024 13:20
Summary
Aerogels are porous and ultralight materials and are presented as a promising option in the treatment of wounds. They, especially those of biological basis such as cellulose derivatives, have unique properties such as high permeability and biocompatibility, creating an ideal environment for tissue regeneration. The preparation of aerogels by drying with supercritical CO2, an ecological and safe method, allows the suitable for biomedical applications. The incorporation into these aerogels of active compounds such as curcumin, a polyphenol with antioxidant and anti-inflammatory properties, offers an innovative approach to improve tissue regeneration and reduce complications linked to wounds. In this work, methylcellulose aerogels loaded with curcumin were manufactured using supercritical CO2 drying technique. In turn, the sterilization of the materials with supercritical CO2 was explored, evaluating its impact on the textural properties and antioxidant activity of curcumin. In this way, the optimal preparation protocol was established, considering the order of the steps and the most appropriate sterilization method.
Aerogels are porous and ultralight materials and are presented as a promising option in the treatment of wounds. They, especially those of biological basis such as cellulose derivatives, have unique properties such as high permeability and biocompatibility, creating an ideal environment for tissue regeneration. The preparation of aerogels by drying with supercritical CO2, an ecological and safe method, allows the suitable for biomedical applications. The incorporation into these aerogels of active compounds such as curcumin, a polyphenol with antioxidant and anti-inflammatory properties, offers an innovative approach to improve tissue regeneration and reduce complications linked to wounds. In this work, methylcellulose aerogels loaded with curcumin were manufactured using supercritical CO2 drying technique. In turn, the sterilization of the materials with supercritical CO2 was explored, evaluating its impact on the textural properties and antioxidant activity of curcumin. In this way, the optimal preparation protocol was established, considering the order of the steps and the most appropriate sterilization method.
Direction
GARCIA GONZALEZ, CARLOS ALBERTO (Tutorships)
López Iglesias, Clara (Co-tutorships)
Iglesias Mejuto, Ana (Co-tutorships)
GARCIA GONZALEZ, CARLOS ALBERTO (Tutorships)
López Iglesias, Clara (Co-tutorships)
Iglesias Mejuto, Ana (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Master Dissertation
Authorship
M.T.A.B.
Master in Drug Research and Development
M.T.A.B.
Master in Drug Research and Development
Defense date
09.23.2024 10:00
09.23.2024 10:00
Summary
Glioblastoma (GB) is one of the most aggressive and invasive brain tumours, with a median survival of approximately one year in most cases. Despite recent advances in the treatment of these tumours, it remains largely incurable with a poor prognosis. For this reason, it is crucial to develop new therapeutic strategies to combat GB. In this study, we propose the optimization of nanoparticles (NPs) modified with a specific ligand for the blood-brain barrier (BBB) to enhance their transport across this barrier. These NPs are being evaluated as potential systems for the delivery of therapeutic peptides for the treatment of GB. Peptide release studies were conducted, analysing the half-life times in relation to the concentration of cholesterol or polyethylene glycol (PEG) present in the nanoparticles. Additionally, in vitro studies revealed significant changes in cellular uptake as the concentration of the BBB-targeting ligand in the NP formulation and the incubation time increased. These results suggest that the ligand plays a crucial role in the uptake by Neu2A (neuroblast) cells, C8-D1A (astrocytes), and GL-261 (GB cells), with higher uptake observed in the Neu2A and C8-D1A cell lines. Finally, in a C57BL/6 mouse model with GB, the biodistribution of the NPs was studied. The results showed that the presence of the ligand in the NPs significantly increased their accumulation in the brain
Glioblastoma (GB) is one of the most aggressive and invasive brain tumours, with a median survival of approximately one year in most cases. Despite recent advances in the treatment of these tumours, it remains largely incurable with a poor prognosis. For this reason, it is crucial to develop new therapeutic strategies to combat GB. In this study, we propose the optimization of nanoparticles (NPs) modified with a specific ligand for the blood-brain barrier (BBB) to enhance their transport across this barrier. These NPs are being evaluated as potential systems for the delivery of therapeutic peptides for the treatment of GB. Peptide release studies were conducted, analysing the half-life times in relation to the concentration of cholesterol or polyethylene glycol (PEG) present in the nanoparticles. Additionally, in vitro studies revealed significant changes in cellular uptake as the concentration of the BBB-targeting ligand in the NP formulation and the incubation time increased. These results suggest that the ligand plays a crucial role in the uptake by Neu2A (neuroblast) cells, C8-D1A (astrocytes), and GL-261 (GB cells), with higher uptake observed in the Neu2A and C8-D1A cell lines. Finally, in a C57BL/6 mouse model with GB, the biodistribution of the NPs was studied. The results showed that the presence of the ligand in the NPs significantly increased their accumulation in the brain
Direction
ALVAREZ CASTRO, EZEQUIEL (Tutorships)
Hervella Lorenzo, Pablo (Co-tutorships)
IGLESIAS REY, RAMON (Co-tutorships)
ALVAREZ CASTRO, EZEQUIEL (Tutorships)
Hervella Lorenzo, Pablo (Co-tutorships)
IGLESIAS REY, RAMON (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Evaluation of the use of coccoliths as carriers of alendronate in bone applications
Authorship
G.R.G.V.
Master in Drug Research and Development
G.R.G.V.
Master in Drug Research and Development
Defense date
09.23.2024 10:20
09.23.2024 10:20
Summary
Bone tissue regeneration is a complex process involving multiple cellular and molecular factors, posing a challenge for regenerative medicine. The development of implantable biomaterials with osteogenic capacity and incorporating active principles for local release represents a suitable alternative for managing bone pathologies such as osteoporosis. In this context, coccoliths, mineralized structures produced by marine organisms like Emiliania huxleyi, primarily composed of calcium carbonate, exhibit favorable properties for inducing bone mineralization. On the other hand, alendronate, a widely used antiresorptive drug in the treatment of osteoporosis, is known for inhibiting osteoclastic activity and increasing bone mineral density. This study evaluates, for the first time, the use of coccoliths as carriers of alendronate, investigating their physicochemical properties and their capacity to adsorb and release the drug. The results indicate that coccoliths can adsorb up to 70% of the employed alendronate, although only 40% of the drug is released in the short term, suggesting a strong affinity between alendronate and the calcium carbonate matrix. This affinity results in a controlled release profile that could have significant clinical applications, facilitating the development of more effective therapies for bone regeneration by improving treatment efficiency and reducing side effects associated with the systemic administration of bisphosphonates.
Bone tissue regeneration is a complex process involving multiple cellular and molecular factors, posing a challenge for regenerative medicine. The development of implantable biomaterials with osteogenic capacity and incorporating active principles for local release represents a suitable alternative for managing bone pathologies such as osteoporosis. In this context, coccoliths, mineralized structures produced by marine organisms like Emiliania huxleyi, primarily composed of calcium carbonate, exhibit favorable properties for inducing bone mineralization. On the other hand, alendronate, a widely used antiresorptive drug in the treatment of osteoporosis, is known for inhibiting osteoclastic activity and increasing bone mineral density. This study evaluates, for the first time, the use of coccoliths as carriers of alendronate, investigating their physicochemical properties and their capacity to adsorb and release the drug. The results indicate that coccoliths can adsorb up to 70% of the employed alendronate, although only 40% of the drug is released in the short term, suggesting a strong affinity between alendronate and the calcium carbonate matrix. This affinity results in a controlled release profile that could have significant clinical applications, facilitating the development of more effective therapies for bone regeneration by improving treatment efficiency and reducing side effects associated with the systemic administration of bisphosphonates.
Direction
LANDIN PEREZ, MARIANA (Tutorships)
DIAZ RODRIGUEZ, PATRICIA (Co-tutorships)
LANDIN PEREZ, MARIANA (Tutorships)
DIAZ RODRIGUEZ, PATRICIA (Co-tutorships)
Court
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Laguna Francia, Mª de los Reyes (Chairman)
DIAZ GOMEZ, LUIS ANTONIO (Secretary)
FERNANDEZ RODRIGUEZ, Ma DEL PILAR (Member)
Green hydrogen production via gas-phase photothermal catalysis
Authorship
A.C.G.
Master in Nanoscience and Nanotechnology
A.C.G.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 12:30
07.16.2024 12:30
Summary
In this Master Thesis, the influence of Cu metal molecules (M-M) deposited on cerium oxide (CeO2) for H2 generation from the dissociation of water molecule using photothermal catalytic water-splitting (WS) is studied. In order to carry out this project, different loading deposited on CeO2 and two different flux of water will be studied. The generated H2 is analysed with gases chromatography and mass spectrometry online. This project has achieved a Cu M-M deposited on CeO2 (Cu M-M/CeO2) six times more active catalyst in front of the CeO2 blank, for WS reaction in same conditions. Cu M-M/CeO2 had a production of 0,340 mg of H2 with the less loaded catalyst (0,1%), as well as 0,500 mg of H2 with the highest loading (1%). Keeping the reaction conditions, only reducing water flux, the Cu M-M/CeO2 (0,1% loading) production descend to 0,260 mg of H2. Despites the use of M-M in this catalysis is not completely developed and this thesis results are a good point to continue improving these new materials in photocatalysis.
In this Master Thesis, the influence of Cu metal molecules (M-M) deposited on cerium oxide (CeO2) for H2 generation from the dissociation of water molecule using photothermal catalytic water-splitting (WS) is studied. In order to carry out this project, different loading deposited on CeO2 and two different flux of water will be studied. The generated H2 is analysed with gases chromatography and mass spectrometry online. This project has achieved a Cu M-M deposited on CeO2 (Cu M-M/CeO2) six times more active catalyst in front of the CeO2 blank, for WS reaction in same conditions. Cu M-M/CeO2 had a production of 0,340 mg of H2 with the less loaded catalyst (0,1%), as well as 0,500 mg of H2 with the highest loading (1%). Keeping the reaction conditions, only reducing water flux, the Cu M-M/CeO2 (0,1% loading) production descend to 0,260 mg of H2. Despites the use of M-M in this catalysis is not completely developed and this thesis results are a good point to continue improving these new materials in photocatalysis.
Direction
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Tutorships)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Tutorships)
Court
TABOADA ANTELO, PABLO (Chairman)
Polavarapu , Lakshminarayana (Secretary)
Riveiro Rodríguez, Antonio (Member)
TABOADA ANTELO, PABLO (Chairman)
Polavarapu , Lakshminarayana (Secretary)
Riveiro Rodríguez, Antonio (Member)
Development of a biocompatible platform for cancer theragnostics
Authorship
Y.H.L.
Master in Nanoscience and Nanotechnology
Y.H.L.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 10:00
07.16.2024 10:00
Summary
In the present work, the synthesis of hybrid nanoparticles for cancer teragnostics was performed. Specifically, polymeric gelatin nanoparticles (GNPs) were synthesized and characterized in which the drug temozolomide, a first-generation drug used to treat brain tumors such as glioblastoma, and superparamagnetic nanoparticles as a contrast agent for magnetic resonance bioimaging were encapsulated. Superparamagnetic iron oxide nanoparticles (MNP) were synthesized using a methodology of thermal decomposition of organometallic precursors. Once the syntheses of the different nanoparticles were carried out, the structural and physicochemical characterization was performed using different experimental techniques. Hydrodynamic sizes and surface load were determined by DLS and Doppler laser anenometry, respectively. The morphology and size of the particles were analyzed by scanning electron microscopy (SEM), demonstrating that they have an ideal size and stability for biomedical applications. In addition, the analysis of the magnetothermic properties such as saturation magnetization and blocking temperature of the MNPs encapsulated in GNPs was performed. On the other hand, the release profile of the hybric particles created using a model such a as Niles Red was analyzed. Finally, in vitro biological studies were carried out to preliminarily analyze cell viability and internalization of the theragnostic platform.
In the present work, the synthesis of hybrid nanoparticles for cancer teragnostics was performed. Specifically, polymeric gelatin nanoparticles (GNPs) were synthesized and characterized in which the drug temozolomide, a first-generation drug used to treat brain tumors such as glioblastoma, and superparamagnetic nanoparticles as a contrast agent for magnetic resonance bioimaging were encapsulated. Superparamagnetic iron oxide nanoparticles (MNP) were synthesized using a methodology of thermal decomposition of organometallic precursors. Once the syntheses of the different nanoparticles were carried out, the structural and physicochemical characterization was performed using different experimental techniques. Hydrodynamic sizes and surface load were determined by DLS and Doppler laser anenometry, respectively. The morphology and size of the particles were analyzed by scanning electron microscopy (SEM), demonstrating that they have an ideal size and stability for biomedical applications. In addition, the analysis of the magnetothermic properties such as saturation magnetization and blocking temperature of the MNPs encapsulated in GNPs was performed. On the other hand, the release profile of the hybric particles created using a model such a as Niles Red was analyzed. Finally, in vitro biological studies were carried out to preliminarily analyze cell viability and internalization of the theragnostic platform.
Direction
TABOADA ANTELO, PABLO (Tutorships)
VELASCO RODRIGUEZ, BRENDA (Co-tutorships)
TABOADA ANTELO, PABLO (Tutorships)
VELASCO RODRIGUEZ, BRENDA (Co-tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
Development and in vitro testing of protamine nanoparticles for drug delivery and their association with pollen microcapsules.
Authorship
I.M.R.
Master in Nanoscience and Nanotechnology
I.M.R.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 10:30
07.16.2024 10:30
Summary
Tuberculosis is a lung disease with a high mortality rate worldwide. Currently, antibacterial therapies have two problems. When administered orally, they produce systemic side effects that would be avoidable if administered in the lungs. Two, the number of antibiotic-resistant bacteria is increasing, Mycobaterium tuberculosis being one of them. This bacterium, responsible for tuberculosis, infects and replicates preferentially within pulmonary macrophages. As a possible antibacterial strategy, protamine nanocapsules (NCs) loaded with rifabutin, an antituberculosis drug, were formulated. By coupling these NCs with a suitable vehicle, they can be administered via the pulmonary route. The vehicle of choice is based on purified chamomile (Matricaria chamomilla) pollen grains, following a purification protocol designed by the research group. The delivery systems were characterised in terms of their physicochemical properties and their interaction with the immune system was evaluated. In these studies, it was observed that there is no activation of dendritic cells when they come into contact with the purified and semi-purified pollen grains. In addition, the pollen grains are able to increase the internalisation of the nanocapsules in RAW 264.7 macrophages, being these pollen grains a good vehicle acting at different stages of the administration and release of the formulation.
Tuberculosis is a lung disease with a high mortality rate worldwide. Currently, antibacterial therapies have two problems. When administered orally, they produce systemic side effects that would be avoidable if administered in the lungs. Two, the number of antibiotic-resistant bacteria is increasing, Mycobaterium tuberculosis being one of them. This bacterium, responsible for tuberculosis, infects and replicates preferentially within pulmonary macrophages. As a possible antibacterial strategy, protamine nanocapsules (NCs) loaded with rifabutin, an antituberculosis drug, were formulated. By coupling these NCs with a suitable vehicle, they can be administered via the pulmonary route. The vehicle of choice is based on purified chamomile (Matricaria chamomilla) pollen grains, following a purification protocol designed by the research group. The delivery systems were characterised in terms of their physicochemical properties and their interaction with the immune system was evaluated. In these studies, it was observed that there is no activation of dendritic cells when they come into contact with the purified and semi-purified pollen grains. In addition, the pollen grains are able to increase the internalisation of the nanocapsules in RAW 264.7 macrophages, being these pollen grains a good vehicle acting at different stages of the administration and release of the formulation.
Direction
CSABA , NOEMI STEFANIA (Tutorships)
CSABA , NOEMI STEFANIA (Tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
Master's Thesis
Authorship
L.O.V.
Master in Nanoscience and Nanotechnology
L.O.V.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 11:30
07.16.2024 11:30
Summary
The development of nanoparticles (NPs) that contain and imitate biological structures and patterns, currently called biomimetics, offers the possibility of generating systems that specifically and actively interact with cells and tissues. These NPs have great potential to target specific biological targets where they can perform a function, for example, delivery of a cargo into the cell. This work focuses on the development and study of various biomimetic NPs, artificial (liposomes) and semi-artificial NPs directly derived from cells (cellsomes [CSMs]) with the objective of evaluating their ability to function as cellular delivery systems based on their biomolecular composition compared to natural NPs such as exosomes. To this end, its toxicity and internalization capacity in adenocarcinoma tumor cells (A549) were studied. Furthermore, the encapsulation of a metal-organic network (MOF) of zirconium (PCN-224) in biomimetic systems was studied as an alternative functionalization strategy. The results showed that the most successful biomimetic systems were those that presented a protein composition more similar to the target cells (exosomes and liposomes enriched with membrane proteins). Finally, the encapsulated PCN-224 incubation assay showed no differences compared to controls beyond a reduction in cell death. Therefore, further experiments would be necessary to determine the levels of cellular internalization in this case.
The development of nanoparticles (NPs) that contain and imitate biological structures and patterns, currently called biomimetics, offers the possibility of generating systems that specifically and actively interact with cells and tissues. These NPs have great potential to target specific biological targets where they can perform a function, for example, delivery of a cargo into the cell. This work focuses on the development and study of various biomimetic NPs, artificial (liposomes) and semi-artificial NPs directly derived from cells (cellsomes [CSMs]) with the objective of evaluating their ability to function as cellular delivery systems based on their biomolecular composition compared to natural NPs such as exosomes. To this end, its toxicity and internalization capacity in adenocarcinoma tumor cells (A549) were studied. Furthermore, the encapsulation of a metal-organic network (MOF) of zirconium (PCN-224) in biomimetic systems was studied as an alternative functionalization strategy. The results showed that the most successful biomimetic systems were those that presented a protein composition more similar to the target cells (exosomes and liposomes enriched with membrane proteins). Finally, the encapsulated PCN-224 incubation assay showed no differences compared to controls beyond a reduction in cell death. Therefore, further experiments would be necessary to determine the levels of cellular internalization in this case.
Direction
DEL PINO GONZALEZ DE LA HIGUERA, PABLO ALFONSO (Tutorships)
Pérez Potti, André (Co-tutorships)
DEL PINO GONZALEZ DE LA HIGUERA, PABLO ALFONSO (Tutorships)
Pérez Potti, André (Co-tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
Comparison of Two PLGA Nanoparticle Fabrication Methods and Evaluation of the Photothermal Efficiency of Au Nanocores and PLGA Nanoparticles with ICG
Authorship
L.V.C.
Master in Nanoscience and Nanotechnology
L.V.C.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 12:30
07.16.2024 12:30
Summary
Nanomedicine is an emerging field that combines nanotechnology and biomedical sciences in order to harness existing properties at the nanoscale to innovate in healthcare, enabling early detection and improved treatment and monitoring of complex diseases such as cancer. This is because nanotechnology manipulates matter at the atomic level, creating nanomaterials with properties that do not exist at the macroscopic scale and/or giving rise to unknown phenomena. Among these, photoactivatable nanoparticles (NPs), such as gold (Au) nano-shells and PLGA NPs incorporating the indocyanine green probe (ICG), are key in laser-activated thermal treatments by converting light energy into thermal energy, as well as being used in the controlled release of drugs. For their synthesis, the microfluidic technique is of interest, which offers uniformity and precision, overcoming the limitations of conventional methods such as batch synthesis, and standing out for the possibility of continuous production and scalability. These nanoplatforms allow both diagnosis and treatment of diseases by phototherapies, such as photothermia and photodynamics, and hyperthermia, using NIR light. The rationale is based on the fact that tumour cells are more sensitive to temperatures of 40-45 degrees than healthy cells, which allows specific treatments to be carried out without damaging the latter. This fact, together with the integration of microfluidics to obtain them, represents a significant advance in terms of optimising formulations and treatments.
Nanomedicine is an emerging field that combines nanotechnology and biomedical sciences in order to harness existing properties at the nanoscale to innovate in healthcare, enabling early detection and improved treatment and monitoring of complex diseases such as cancer. This is because nanotechnology manipulates matter at the atomic level, creating nanomaterials with properties that do not exist at the macroscopic scale and/or giving rise to unknown phenomena. Among these, photoactivatable nanoparticles (NPs), such as gold (Au) nano-shells and PLGA NPs incorporating the indocyanine green probe (ICG), are key in laser-activated thermal treatments by converting light energy into thermal energy, as well as being used in the controlled release of drugs. For their synthesis, the microfluidic technique is of interest, which offers uniformity and precision, overcoming the limitations of conventional methods such as batch synthesis, and standing out for the possibility of continuous production and scalability. These nanoplatforms allow both diagnosis and treatment of diseases by phototherapies, such as photothermia and photodynamics, and hyperthermia, using NIR light. The rationale is based on the fact that tumour cells are more sensitive to temperatures of 40-45 degrees than healthy cells, which allows specific treatments to be carried out without damaging the latter. This fact, together with the integration of microfluidics to obtain them, represents a significant advance in terms of optimising formulations and treatments.
Direction
TABOADA ANTELO, PABLO (Tutorships)
TOPETE CAMACHO, ANTONIO (Co-tutorships)
TABOADA ANTELO, PABLO (Tutorships)
TOPETE CAMACHO, ANTONIO (Co-tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
Solid Lipid Nanoparticles and Sporopollenin Microcapsules for pulmonary administration of the antibiotics isoniazid and rifabutin
Authorship
A.E.L.
Master in Nanoscience and Nanotechnology
A.E.L.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 13:00
07.16.2024 13:00
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of global mortality, underscoring the urgency of developing new treatments for this infectious disease. Pulmonary administration of anti-TB antibiotics represents a promising alternative to traditional oral administration, as it directly targets alveolar macrophages (AM), where M. tuberculosis bacilli reside. This study focuses on the development of solid lipid nanoparticles (SLNS) and the use of sporopollenin capsules purified from Matricaria chamomilla pollen, loaded with isoniazid (INH) and rifabutin (RFB), two key antibiotics in TB treatment, designed for pulmonary administration. Initially, the purification process of pollen and the preparation of SLNS were optimized, followed by a physicochemical and morphological characterization of both systems. Subsequently, the drugs were encapsulated using methods such as incubation -and rotary evaporation, with release profiles evaluated to determine encapsulation efficiency (EE) and drug loading (DL). All tested formulations exhibited a rapid initial release, followed by a slow and exponential release from 4 hours up to 48 hours. Additionally, the percentages of EE and DL were high. Moreover, macrophage cell assays were conducted to evaluate the efficacy of the proposed treatment, demonstrating that none of the designed formulations were toxic to macrophages and that there was a high uptake of the formulations by these cells.
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of global mortality, underscoring the urgency of developing new treatments for this infectious disease. Pulmonary administration of anti-TB antibiotics represents a promising alternative to traditional oral administration, as it directly targets alveolar macrophages (AM), where M. tuberculosis bacilli reside. This study focuses on the development of solid lipid nanoparticles (SLNS) and the use of sporopollenin capsules purified from Matricaria chamomilla pollen, loaded with isoniazid (INH) and rifabutin (RFB), two key antibiotics in TB treatment, designed for pulmonary administration. Initially, the purification process of pollen and the preparation of SLNS were optimized, followed by a physicochemical and morphological characterization of both systems. Subsequently, the drugs were encapsulated using methods such as incubation -and rotary evaporation, with release profiles evaluated to determine encapsulation efficiency (EE) and drug loading (DL). All tested formulations exhibited a rapid initial release, followed by a slow and exponential release from 4 hours up to 48 hours. Additionally, the percentages of EE and DL were high. Moreover, macrophage cell assays were conducted to evaluate the efficacy of the proposed treatment, demonstrating that none of the designed formulations were toxic to macrophages and that there was a high uptake of the formulations by these cells.
Direction
REMUÑAN LOPEZ, MARIA DEL CARMEN (Tutorships)
REMUÑAN LOPEZ, MARIA DEL CARMEN (Tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
Optimization of gene activated matrices based on fibrin.
Authorship
C.F.S.
Master in Nanoscience and Nanotechnology
C.F.S.
Master in Nanoscience and Nanotechnology
Defense date
07.16.2024 13:30
07.16.2024 13:30
Summary
Gene activated matrices (GAMs) have emerged as an improvement over conventional matrices. Among GAMs, those based on fibrin are widely used due to their viscoelastic and biocompatible properties, but their main disadvantage is their rapid degradation. In the present work we intend to test the potential usefulness of incorporating chitosan into fibrin-based GAMs in order to increase their resistance to degradation and their durability over time. Increasing these properties is expected to favor the sustained release of the recombinant protein encoded by the genetic material contained in the matrix. Different compositions for the elaboration of the matrices were tested and a viability test, a study of their degradation over time and the transfective capacity of the selected prototypes was analyzed.
Gene activated matrices (GAMs) have emerged as an improvement over conventional matrices. Among GAMs, those based on fibrin are widely used due to their viscoelastic and biocompatible properties, but their main disadvantage is their rapid degradation. In the present work we intend to test the potential usefulness of incorporating chitosan into fibrin-based GAMs in order to increase their resistance to degradation and their durability over time. Increasing these properties is expected to favor the sustained release of the recombinant protein encoded by the genetic material contained in the matrix. Different compositions for the elaboration of the matrices were tested and a viability test, a study of their degradation over time and the transfective capacity of the selected prototypes was analyzed.
Direction
GARCIA FUENTES, MARCOS (Tutorships)
GARCIA FUENTES, MARCOS (Tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
IGLESIAS REY, RAMON (Secretary)
González Fernández, Pío Manuel (Member)