Person: Vallet Regí, María Dulce Nombre
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First Name
María Dulce Nombre
Last Name
Vallet Regí
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Inorgánica
Identifiers
92 results
Search Results
Now showing 1 - 10 of 92
Item Antimycobacterial effect of selenium nanoparticles on Mycobacterium tuberculosis.(Frontiers Microbiology, 2020) Estévez Sánchez, Héctor; Palacios, Ainhoa; Gil, David; Anguita, Juan; Vallet Regí, María Dulce Nombre; González Ortiz, Blanca; Prados Rosales, Rafael; Luque-García, José L.Tuberculosis remains the leading cause of death from a single infection agent worldwide. In recent years, the occurrence of tuberculosis cases caused by drug-resistant strains has spread, and is expected to continue to grow. Therefore, the development of new alternative treatments to the use of antibiotics is highly important. In that sense, nanotechnology can play a very relevant role, due to the unique characteristics of nanoparticles. In fact, different types of nanoparticles have already been evaluated both as potential bactericides and as efficient drug delivery vehicles. In this work, the use of selenium nanoparticles has been evaluated to inhibit the growth of two types of mycobacteria: Mycobacterium smegmatis and Mycobacterium tuberculosis. The results showed that selenium nanoparticles are able to inhibit the growth of both types of mycobacteria by damaging their cell envelope integrity. These results open a new opportunity for the use of this type of nanoparticles as antimycobacterial agents by themselves, or for the development of novel nanosystems that combine the action of these nanoparticles with other drugs.Item Effects of ipriflavone-loaded mesoporous nanospheres on the differentiation of endothelial cells and their modulation by macrophages.(Nanomaterials, 2021) Casarrubios Molina, Laura; Polo Montalvo, Alberto; Serrano, María Concepción; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaAngiogenic biomaterials for bone repair are being designed to promote vascularization and optimize tissue regeneration. The use of nanoparticles of bioactive materials loaded with different drugs represents an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. Ipriflavone (IP) prevents osteoporosis by inhibiting osteoclast activity and promoting preosteoblast differentiation into mature osteoblasts. Since endothelial progenitor cells (EPCs) are involved in the formation of blood vessels which are necessary for tissue regeneration, the isolation and characterization of porcine EPCs have been carried out in this work to evaluate the in vitro effects of unloaded (NanoMBGs) and IP-loaded nanospheres (NanoMBG-IPs) designed to stimulate osteogenesis. Because different signals between vascular and nonvascular cells are also essential to initiate angiogenic events, the potential modulating role of macrophages has been also evaluated by studying the expression of vascular endothelial growth factor receptor 2 (VEFGR2) as a specific marker for EPC differentiation under different culture conditions: a) EPCs in monoculture treated with NanoMBGs or NanoMBG-IPs, b) EPCs treated with conditioned media from basal, proinflammatory M1 and reparative M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, c) EPCs cocultured with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and d) EPCs cocultured with M2d angiogenic macrophages. Moreover, the endocytic mechanisms by which these nanospheres are incorporated by EPCs have been identified by using six endocytosis inhibitors (i.e. wortmannin, genistein, cytochalasin B, cytochalasin D, phenylarsine oxide and chlorpromazine) and before the addition of NanoMBGs labeled with fluorescein isothiocyanate. The results evidence the great potential of both NanoMBGs and NanoMBG-IPs to enhance VEFGR2 expression, directly related to angiogenesis, after intracellular incorporation by EPCs through different endocytic mechanisms including clathrin-dependent endocytosis, as the main entry mechanism, but also phagocytosis and caveolae-mediated uptake. The treatment of EPCs with culture media from basal, M1 and M2 macrophages and the development of cocultures of EPCs with macrophages in the absence and presence of these nanomaterials have also confirmed the maintenance of their angiogenic effect on EPCs even in the presence of phagocytic cells.Item Effect of gold nanostars plus amikacin against cabapenem-resistant Klebsiella pneumoniae biofilm.(Biology, 2022) Aguilera Correa, John Jairo; García Álvarez, Rafaela; Mediero Muñoz, Aránzazu; Esteban, Jaime; Vallet Regí, María Dulce Nombre(1) Background: Carbapenem-resistant Klesiella pneumoniae (CR-KP) infection rates depict an almost pre-antibiotic scenario since the pipeline for effective antibiotics against this pathogen has been almost entirely depleted. This study aims to evaluate the antibacterial effect of gold nanostars (GNS) alone or associated with some of the most widely used antibiotics for the treatment of CR-KP strains, i.e., meropenem or amikacin, on both planktonic and sessile forms. Additionally, we measured the effect of GNS on cell proliferation and biocompatibility in invertebrate in vivo models. (2) Materials and methods: GNS were made from gold seeds grown using a seeded-growth surfactant-free method assisted by silver ions and functionalized with mercapto-poly(ethylene glycol)amino by ligand exchange. The antimicrobial capacity, effect on cell proliferation, and biocompatibility of the most effective combination was evaluated in a Galleria mellonella model. (3) Results:The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were 80 and 160 µM of GNS for all strains, respectively. The minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were >320 µM of GNS for both. A synergy was found between GNS and amikacin. Larvae administered GNS plus amikacin were found to tolerate the treatment well, which prevented infection. (4) Conclusions: GNS are a promising anti-CR-KP nanomaterial.Item Evolution of Biomaterials(Frontiers in Materials, 2022) Vallet Regí, María Dulce NombreThere is a clear need for increasingly versatile and effective implantable biomaterials, and to train qualified personnel for research and development in the field of biomaterials design and manufacturing. In all these implantable biomaterials, science and technology are imposing new designs with combinations of new biomaterials, new coatings, and new design and manufacturing technologies (biomimetic biomaterials, functional biomaterials, nanotechnology, finite element modeling, additive manufacturing, 3D printing, tissue engineering, and drug delivery) that will revolutionize the field of implants in the short term. Biomaterials are part of biomedical engineering and bring together knowledge from the world of science, engineering, biology, and medicine, being a multidisciplinary field where borders have no place.Item Mesoporous bioactive glasses for regenerative medicine.(Materials Today Bio, 2021) Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.Stem cells are the central element of regenerative medicine (RM). However, in many clinical applications the use of scaffolds fabricated with biomaterials is required. In this sense, mesoporous bioactive glasses (MBGs) are going to play an important role in bone regeneration because their striking textural properties, quick bioactive response and biocompatibility. As the other bioactive glasses, MBGs are mainly formed by silicon, calcium and phosphorus oxides whose ions play an important role in cell proliferation as well as in homeostasis and bone remodeling process. A common improvement of bioactive glasses for RM is by adding small amounts of oxides of elements that confer them additional biological capacities, including osteogenic, angiogenic, antibacterial, anti-inflammatory, haemostatic or anticancer properties. Moreover, MBGs are versatile in terms of the different ways in which they can be processed such as scaffolds, fibers, coatings or nanoparticles. MBGs are unique because their textural properties are so high that they still exhibit outstanding bioactive responses even after adding extra inorganic ions or being processed as scaffolds or nanoparticles. Moreover, they can be further improved by loading with biomolecules, drugs and stem cells. This article reviews the state of the art and future perspectives of MBGs in the field of RM of hard tissues.Item Arabic gum plus colistin coated moxifloxacin-loaded nano particles forthe treatment of bone infection caused by Escherichia coli(Acta Biomaterialia, 2021) Aguilera Correa, John Jairo; Gisbert Garzarán, Miguel; Mediero Muñoz, Aránzazu; Carias Calix, R.A; Jiménez Jiménez, Carla; Esteban, Jaime; Vallet Regí, María Dulce NombreOsteomyelitis is an inflammatory process of bone and bone marrow that may even lead topatient death. Even though this disease is mainly caused by Gram-positive organisms, the proportion of bone infections caused by Gram-negative bacteria, such as Escherichia coli, has significantly increased in recent years. In this work, mesoporous silica nanoparticles have been employed as a platform to engineer a nanomedicine able to eradicate E. coli- related bone infections. For that purpose, the nanoparticles have been loaded with moxifloxacin and further functionalized with Arabic gum and colistin (AG+CO-coated MX-loaded MSNs). The nanosystem demonstrated high affinity toward E. coli biofilm matrix, thanks to AG coating, and marked antibacterial effect because of the bactericidal effect of moxifloxacin and the disaggregating effect of colistin. AG+CO-coated MX-loaded MSNs were able to eradicate the infection developed on a trabecular bone in vitro and showed pronounced antibacterial efficacy in vivo against an osteomyelitis provoked by E. coli. Furthermore, AG+CO-coated MX-loaded MSNs were shown to be essentially non-cytotoxic with only slight effect on cell proliferation and mild hepatotoxicity, which might be attributed to the nature of both antibiotics. In view of these results, these nanoparticles may be considered as a promising treatment for bone infections caused by enterobacteria, such as E. coli, and introduce a general strategy against bone infections based on the implementation of antibiotics with different but complementary activity into a single nanocarrier.Item Mesoporous Silica Nanoparticles as Carriers for Therapeutic Biomolecules.(Pharmaceutics, 2020) Castillo, Rafael R.; Lozano Borregón, Daniel; Vallet Regí, María Dulce NombreThe enormous versatility of mesoporous silica nanoparticles permits the creation of a large number of nanotherapeutic systems for the treatment of cancer and many other pathologies. In addition to the controlled release of small drugs, these materials allow a broad number of molecules of a very dièerent nature and sizes. In this review, we focus on biogenic species with therapeutic abilities (proteins, peptides, nucleic acids, and glycans), as well as how nanotechnology, in particular silica-based materials, can help in establishing new and more efficient routes for their administration. Indeed, since the applicability of those combinations of mesoporous silica with bio(macro)molecules goes beyond cancer treatment, we address a classification based on the type of therapeutic action. Likewise, as illustrative content, we highlight the most typical issues and problems found in the preparation of those hybrid nanotherapeutic materials.Item Cu-doped hollow bioactive glass nanoparticles for bone infec-tion treatment(Pharmaceutics, 2022) Jiménez Holguín, Javier; Sánchez Salcedo, Sandra; Cicuéndez Maroto, Mónica; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.In search of new approaches to treat bone infection and prevent drug resistance development, a nanosystem based on hollow bioactive glass nanoparticles (HBGN) of composition 79.5SiO2–(18-x)CaO–2.5P2O5–xCuO (x = 0, 2.5 or 5 mol-% CuO) was developed. The objective of the study was to evaluate the capacity of the HBGN to be used as nanocarriers of the broad-spectrum anti-biotic danofloxacin and source of bactericidal Cu2+ ions. Core-shell nanoparticles with specific surface areas close to 800 m2/g and pore volumes around 1 cm3/g were obtained by using hexa-decyltrimethylammonium bromide (CTAB) and poly (styrene)-block-poly (acrylic acid) (PS-b-PAA) as structure-directing agents. Flow cytometry studies showed the cytocompatibility of the nanoparticles in MC3T3-E1 pre-osteoblastic cell cultures. Ion release studies confirmed the release of non-cytotoxic concentrations of Cu2+ ions within the therapeutic range. Moreover, it was shown that the inclusion of copper in the system resulted in a more gradual release of da-nofloxacin that was extended over one week. The bactericidal activity of the nanosystem was evaluated with E. coli and S. aureus strains. Nanoparticles with copper were not able to reduce bacterial viability by themselves and Cu-free HBGN failed to reduce bacterial growth, despite releasing higher antibiotic concentrations. However, HBGN enriched with copper and da-nofloxacin drastically reduced bacterial growth in sessile, planktonic and biofilm states, which was attributed to a synergistic effect between the action of Cu2+ ions and danofloxacin. There-fore, the nanosystem here investigated is a promising candidate as an alternative for the local treatment of bone infections.Item Multifunctional antibiotic- and zinc-containing mesoporous bioactive glass scaffolds to fight bone infection.(Acta Biomaterialia, 2020) Heras, Clara; Jiménez Holguín, Javier; Doadrio Villarejo, Antonio Luis; Vallet Regí, María Dulce Nombre; Sánchez Salcedo, Sandra; Salinas Sánchez, Antonio J.Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also includes the development of osteogenic and antibacterial biomaterials to treat the emergence of possible infection processes arising from surgery. This study evaluates the antibacterial properties of gelatin-coated meso-macroporous scaffolds based on the bioactive glass 80%SiO2–15%CaO–5%P2O5 (mol-%) before (BL-GE) and after being doped with 4% of ZnO (4ZN-GE) and loaded with both saturated and the minimal inhibitory concentrations of one of the antibiotics: levofloxacin (LEVO), vancomycin (VANCO), rifampicin (RIFAM) or gentamicin (GENTA). After physical-chemical characterization of materials, release studies of inorganic ions and antibiotics from the scaffolds were carried out. Moreover, molecular modelling allowed determining the electrostatic potential density maps and the hydrogen bonds of antibiotics and the glass matrix. Antibacterial in vitro studies (in planktonic, inhibition halos and biofilm destruction) with S. aureus and E. coli as bacteria models showed a synergistic effect of zinc ions and antibiotics. The effect was especially noticeable in planktonic cultures of S. aureus with 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and in E. coli cultures with LEVO or GENTA. Moreover, S. aureus biofilms were completely destroyed by 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and the E. coli biofilm total destruction was accomplished with 4ZN-GE scaffolds loaded with GENTA or LEVO. This approach could be an important step in the fight against microbial resistance and provide needed options for bone infection treatment.Item Development and evaluation of copper-containing mesoporous bioactive glasses for bone defects therapy.(Microporous and Mesoporous Materials, 2020) Jiménez Holguín, Javier; Sánchez Salcedo, Sandra; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.Mesoporous bioactive glasses (MBGs) are gaining increasing interest in the design of new biomaterials for bone defects treatment. An important research trend to enhance their biological behavior is the inclusion of moderate amounts of oxides with therapeutical action such as CuO. MBGs with composition (85-x)SiO2–10- CaO–5P2O5–xCuO (x = 0, 2.5 or 5 mol-%) were synthesized, investigating the influence of the CuO content and some synthesis parameters in their properties. Two series were developed; first one used HCl as catalyst and chlorides as CaO and CuO precursors, second one, used HNO3 and nitrates. MBGs of chlorides family exhibited calcium/copper phosphate nanoparticles between 10 and 20 nm in size. Nevertheless, CuO-containing MBGs of nitrates family showed metallic copper nanoparticles larger than 50 nm as well as quicker in vitro bioactive responses. Thus, MBGs of the nitrate series were coated by an apatite-like layer after 24 h soaked in simulated body fluid (SBF) a remarkably short period for a MBG containing 5% of CuO. A model, focused in the location of copper in the glass network, was proposed to relate nanostructure and in vitro behaviour. Moreover, after 24 h soaked in MEM or THB culture media, all the MBGs released therapeutic amounts of Ca2+ and Cu2+ ions. Because the quick bioactive response in SBF, the capacity to host biomolecules in their pores and to release therapeutic concentrations of Ca2+ and Cu2+ ions, MBGs of the nitrate families are proposed as excellent biomaterials for bone regeneration.