Person: Jiménez Holguín, Javier
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First Name
Javier
Last Name
Jiménez Holguín
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
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3 results
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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.