GRUPOS DE INVESTIGACIÓN

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Otros Universidad Complutense de Madrid

Nuestra línea prioritaria se enfoca en: 1- Diseño de vacunas (HisAK70) frente a leishmaniosis . 2- ... y Reposicionamiento de fármacos. Otros patógenos en estudio: Trypanosoma, Giardia, Trichomonas.

FCO. JAVIER CARRIÓN HERRERO

Líneas de Investigación

Inmunología y Control de Zoonosis Desatendidas (Leishmaniosis & enfermedad de Chagas)

La actividad investigadora se centra prioritariamente en el desarrollo de vacunas frente a las leishmaniosis (vacuna multicomponente HisAK70), y en el diseño de nuevas estrategias terapéuticas, basadas en inmunoquimioterapia combinada y reposicionamiento de fármacos. Otros patógenos: Trypanosoma, Giardia, Trichomonas

Proyectos de Investigación

Estrategias quimio-inmunoterapéuticas optimizadas en nanopartículas para el tratamiento de las leishmaniosis cutáneas

Año: 2024
Convocatoria: PID2023-148406OB-I00 MINISTERIO DE CIENCIA

Patentes

Quimera multicomponente para su uso como vacuna frente a la infección por. Leishmania spp en mamiferos

QUIMERA SINTÉTICA MULTIEPITÓPICA COMO VACUNA Y TRATAMIENTO FRENTE A LEISHMANIOSIS EN MAMÍFEROS

Publicaciones

Microbial Matryoshka: Addressing the Relationship between Pathogenic Flagellated Protozoans and Their RNA Viral Endosymbionts (Family Totiviridae)

Three genera of viruses of the family Totiviridae establish endosymbiotic associations with flagellated protozoa responsible for parasitic diseases of great impact in the context of One Health. Giardiavirus, Trichomonasvirus, and Leishmaniavirus infect the protozoa Giardia sp., Trichomonas vaginalis, and Leishmania sp., respectively. In the present work, we review the characteristics of the endosymbiotic relationships established, the advantages, and the consequences caused in mammalian hosts. Among the common characteristics of these double-stranded RNA viruses are that they do not integrate into the host genome, do not follow a lytic cycle, and do not cause cytopathic effects. However, in cases of endosymbiosis between Leishmaniavirus and Leishmania species from the Americas, and between Trichomonasvirus and Trichomonas vaginalis, it seems that it can alter their virulence (degree of pathogenicity). In a mammalian host, due to TLR3 activation of immune cells upon the recognition of viral RNA, uncontrolled inflammatory signaling responses are triggered, increasing pathological damage and the risk of failure of conventional standard treatment. Endosymbiosis with Giardiavirus can cause the loss of intestinal adherence of the protozoan, resulting in a benign disease. The current knowledge about viruses infecting flagellated protozoans is still fragmentary, and more research is required to unravel the intricacies of this three-way relationship. We need to develop early and effective diagnostic methods for further development in the field of translational medicine. Taking advantage of promising biotechnological advances, the aim is to develop ad hoc therapeutic strategies that focus not only on the disease-causing protozoan but also on the virus.https://www.mdpi.com/2306-7381/11/7/321

Antiprotozoal Potential of Cultivated Geranium macrorrhizum Against Giardia duodenalis, Trichomonas gallinae and Leishmania infantum

Plant-derived natural products are an invaluable source of structurally diverse secondary metabolites with ecological and pharmacological significance. Geranium macrorrhizum, a species known for producing essential oils rich in monoterpenoids and sesquiterpenes, has been scarcely explored for its antiparasitic potential. This study represents the first comprehensive evaluation of the antiprotozoal activity of G. macrorrhizum obtained from cultivated plants. Plant material was produced under controlled greenhouse cultivation systems, ensuring high-quality and reproducible metabolite profiles. Essential oils were obtained through hydrodistillation and chemically characterized by Gas Chromatography-Mass Spectrometry (GC–MS). In vitro assays were conducted against Giardia duodenalis, Trichomonas gallinae, and Leishmania infantum to assess antiparasitic efficacy and cytotoxicity. The results demonstrated strong activity of essential oils against Trichomonas gallinae, and Leishmania infantum, indicating the relevance of lipophilic compounds—especially germacrone—as key bioactive constituents. Germacrone exhibited strong and selective antiparasitic activity, outperforming its structural analogues. Microscopic analyses revealed distinct parasite-specific morphological alterations, differing from those induced by conventional drugs such as metronidazole and amphotericin B. These findings highlight G. macrorrhizum obtained through biotechnological cultivation as a novel and sustainable source of natural antiprotozoal agents. The study underscores the importance of integrating controlled cultivation with phytochemical and biological evaluation to advance the discovery of innovative bioactive compounds.https://www.mdpi.com/1422-0067/27/2/1125

Fluidity as a key determinant of stability in PEGylated lipid nanoparticles loaded with a TLR7 agonist

TLR7 agonists are low molecular weight immunomodulators that can rapidly diffuse from the site of administration, often leading to undesired systemic inflammatory effects. To mitigate toxicity and broaden therapeutic applicability, imiquimod (IMQ), a widely used TLR7 agonist, was encapsulated in lipid-based nanocarriers (LNCs). A fractional factorial design (24−1) was employed to examine the influence of formulation variables—liquid lipid (LL), solid lipid (SL), lipid molar ratio, and surfactant—on particle size, encapsulation efficiency, colloidal stability, and cytotoxicity in bone marrow-derived macrophages (BMDMs) and erythrocytes. Screening indicated that LL type and SL/LL ratio were the most critical factors affecting both physicochemical and biological properties. Based on these insights, a refined study focused on C10–C18 triglycerides as SL and PEG40-stearate as surfactant, while varying LL (oleic acid or isostearic acid) at two SL/LL molar ratios (2.5:1 and 1:2.5). Structural and biophysical analyses (DSC, SAXS, DPH and Laurdan fluorescence) showed that lipid shell fluidity dictated PEG conformation at the particle surface: rigid shells promoted a hydrated brush-like PEG layer, whereas fluid shells yielded a collapsed, less stable arrangement. The optimal formulation (triglycerides: oleic acid, 2.5:1) generated nanoparticles of 45 nm with efficient IMQ encapsulation and low cytotoxicity. This system effectively reprogrammed BMDMs toward a pro-inflammatory (M1) phenotype, confirmed by gene and cytokine expression. Altogether, these results highlight the importance of formulation design and nanostructural characterization in developing nanocarrier systems that enable safer and more versatile delivery of potent immunotherapeutics such as IMQ.https://www.sciencedirect.com/science/article/pii/S0378517325012815?via%3Dihub

Standardization of canine infections for the development of antileishmanial drugs

Chemotherapy of leishmaniasis, both human and canine, is far from ideal and new antileishmanial drugs are urgently needed. Therapeutic arsenal against the disease is old, of low antileishmanial efficacy and hampered by toxicity issues in some cases. Furthermore, hospitalization required for some drugs, the price of the safer presentations is high and there are growing reports of leishmanial resistance to first line medicines. In addition to human visceral cases, canine infections by Leishmania infantum represent a first order veterinary pathology with dogs being the main reservoir for this zoonotic infection. Thus, dog infections by L. infantum are needed to develop veterinary drugs and are the best surrogate model for human leishmaniasis. Many contributions on the efficacy of new drugs or presentations in dogs have been published but the variety of experimental designs makes comparisons challenging thus reducing their value. Present study offers a comprehensive review of canine experimental infections with visceral Leishmania, with a particular focus on L. infantum. The review encompasses a range of topics, including animal housing, regulatory aspects, ethical considerations, infection methods, follow-up procedures, and outcomes. The final aim of our contribution is to promote the standardization of some experimental procedures to enhance the comparability of the studies performed. This, in turn, is expected to reduce the use of animals and to increase the efficiency of drug discovery and development.https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2026.1754269/full

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Una iniciativa de

Ayuda PTR2024-002951 financiada por

UNION EUROPEA - FONDO EUROPEO DE DESARROLLO REGIONAL

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