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Dive into the research topics where Francisco J. Parra-Ruiz is active.

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Featured researches published by Francisco J. Parra-Ruiz.


Biomaterials | 2014

PHACOS, a functionalized bacterial polyester with bactericidal activity against methicillin-resistant Staphylococcus aureus.

Nina Dinjaski; Mar Fernández-Gutiérrez; Shivaram Selvam; Francisco J. Parra-Ruiz; Susan M. Lehman; Julio San Román; Ernesto García; José Luis García; Andrés J. García; María Auxiliadora Prieto

Biomaterial-associated infections represent a significant clinical problem, and treatment of these microbial infections is becoming troublesome due to the increasing number of antibiotic-resistant strains. Here, we report a naturally functionalized bacterial polyhydroxyalkanoate (PHACOS) with antibacterial properties. We demonstrate that PHACOS selectively and efficiently inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. This ability has been ascribed to the functionalized side chains containing thioester groups. Significantly less (3.2-fold) biofilm formation of S. aureus was detected on PHACOS compared to biofilms formed on control poly(3-hydroxyoctanoate-co-hydroxyhexanoate) and poly(ethylene terephthalate), but no differences were observed in bacterial adhesion among these polymers. PHACOS elicited minimal cytotoxic and inflammatory effects on murine macrophages and supported normal fibroblast adhesion. In vivo fluorescence imaging demonstrated minimal inflammation and excellent antibacterial activity for PHACOS compared to controls in an in vivo model of implant-associated infection. Additionally, reductions in neutrophils and macrophages in the vicinity of sterile PHACOS compared to sterile PHO implant were observed by immunohistochemistry. Moreover, a similar percentage of inflammatory cells was found in the tissue surrounding sterile PHACOS and S. aureus pre-colonized PHACOS implants, and these levels were significantly lower than S. aureus pre-colonized control polymers. These findings support a contact active surface mode of antibacterial action for PHACOS and establish this functionalized polyhydroxyalkanoate as an infection-resistant biomaterial.


Biomacromolecules | 2015

Anticancer and antiangiogenic activity of surfactant-free nanoparticles based on self-assembled polymeric derivatives of vitamin E: Structure-activity relationship

Raquel Palao-Suay; María Rosa Aguilar; Francisco J. Parra-Ruiz; Mar Fernández-Gutiérrez; Juan Parra; Carolina Sánchez-Rodríguez; Ricardo Sanz-Fernández; Laura Rodrigáñez; Julio San Román

α-Tocopheryl succinate (α-TOS) is a well-known mitochondrially targeted anticancer compound, however, it is highly hydrophobic and toxic. In order to improve its activity and reduce its toxicity, new surfactant-free biologically active nanoparticles (NP) were synthesized. A methacrylic derivative of α-TOS (MTOS) was prepared and incorporated in amphiphilic pseudoblock copolymers when copolymerized with N-vinylpyrrolidone (VP) by free radical polymerization (poly(VP-co-MTOS)). The selected poly(VP-co-MTOS) copolymers formed surfactant-free NP by nanoprecipitation with sizes between 96 and 220 nm and narrow size distribution, and the in vitro biological activity was tested. In order to understand the structure-activity relationship three other methacrylic monomers were synthesized and characterized: MVE did not have the succinate group, SPHY did not have the chromanol ring, and MPHY did not have both the succinate group and the chromanol ring. The corresponding families of copolymers (poly(VP-co-MVE), poly(VP-co-SPHY), and poly(VP-co-MPHY)) were synthesized and characterized, and their biological activity was compared to poly(VP-co-MTOS). Both poly(VP-co-MTOS) and poly(VP-co-MVE) presented triple action: reduced cell viability of cancer cells with little or no harm to normal cells (anticancer), reduced viability of proliferating endothelial cells with little or no harm to quiescent endothelial cells (antiangiogenic), and efficiently encapsulated hydrophobic molecules (nanocarrier). The anticancer and antiangiogenic activity of the synthesized copolymers is demonstrated as the active compound (vitamin E or α-tocopheryl succinate) do not need to be cleaved to trigger the biological action targeting ubiquinone binding sites of complex II. Poly(VP-co-SPHY) and poly(VP-co-MPHY) also formed surfactant-free NP that were also endocyted by the assayed cells; however, these NP did not selectively reduce cell viability of cancer cells. Therefore, the chromanol ring of the vitamin E analogues has an important role in the biological activity of the copolymers. Moreover, when succinate moiety is substituted and vitamin E is directly linked to the macromolecular chain through an ester bond, the biological activity is maintained.


Polymer Chemistry | 2013

Smart heparin-based bioconjugates synthesized by a combination of ATRP and click chemistry

Felisa Reyes-Ortega; Francisco J. Parra-Ruiz; Saadyah Averick; Gema Rodríguez; María Rosa Aguilar; Krzysztof Matyjaszewski; Julio San Román

This article describes the synthesis of novel well defined polysaccharide–polymer bioconjugates. Alkyne-containing bioconjugates were prepared using Cu(I) catalyzed azide–alkyne [3 + 2] dipolar cycloaddition, i.e. ‘click’ chemistry between an alkyne functionalized low molecular weight heparin (LMWH) and α-azide functionalized stimuli-responsive copolymers synthesized by atom transfer radical polymerization using Activators Generated by Electron Transfer (AGET). The alkyne functionality was incorporated into the heparin by conducting a high yield amidation of the polysaccharide using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The structure and composition of the novel bioconjugates were confirmed by FTIR, NMR and thermogravimetric analysis (TGA).


Polymer Chemistry | 2016

α-TOS-based RAFT block copolymers and their NPs for the treatment of cancer

Raquel Palao-Suay; María Rosa Aguilar; Francisco J. Parra-Ruiz; Samarendra Maji; Richard Hoogenboom; Nathan A. Rohner; Susan N. Thomas; Julio San Román

α-Tocopheryl succinate (α-TOS) is a well-known mitochondrially targeted anticancer compound. However, a major factor limiting the use of α-TOS is its low solubility in physiological media. To overcome this problem, the aim of this work is the preparation of new polymeric and active α-TOS-based nanovehicle with a precise control over its macromolecular architecture. Reversible addition–fragmentation chain transfer polymerization (RAFT) is used to synthesize an α-TOS amphiphilic block copolymer with highly homogeneous molecular weight and relatively narrow dispersity. Macro-chain transfer agents (macro-CTA) based on poly(ethylene glycol) (PEG) of different molecular weights (MW, ranging from 4.6 to 20 kDa) are used to obtain block copolymers with different hydrophilic/hydrophobic ratios with PEG being the hydrophilic block and a methacrylic derivative of α-tocopheryl succinate (MTOS) being the monomer that formed the hydrophobic block. PEG-b-poly(MTOS) form spherical nanoparticles (NPs) by self-organized precipitation (SORP) or solvent exchange in aqueous media enabling to encapsulate and deliver hydrophobic molecules in their core. The resulting NPs are rapidly endocytosed by cancer cells. The biological activity of the synthesized NPs are found to depend on the MW of PEG, with the NP comprised of the higher MW copolymer resulting in a lower bioactivity due to PEG shielding, inhibiting cellular uptake by endocytosis. Moreover, the biological activity also depends on the MTOS content, as the biological activity increases as a function of MTOS concentration.


International Journal of Pharmaceutics | 2017

Development of advanced biantibiotic loaded bone cement spacers for arthroplasty associated infections

Francisco J. Parra-Ruiz; Álvaro González-Gómez; Mar Fernández-Gutiérrez; Juan Parra; J. García-García; G. Azuara; B. de la Torre; Julia Buján; B. Ibarra; L. Duocastella-Codina; M. Molina-Crisol; Blanca Vázquez-Lasa; J. San Román

The incidence increase of infections in patients with hip or knee implants with resistant pathogens (mainly some S. coagulase-negative and gram positive bacteria) demands advanced antibiotic loaded formulations. In this paper, we report the design of new biantibiotic acrylic bone cements for in situ delivery. They include a last generation antibiotic (daptomycin or linezolid) in combination with vancomycin and are performed based on a novel modification of the Palacos R® acrylic bone cement, which is based on two components, a liquid (methyl methacrylate) and a solid (polymeric phase). Hence, the solid component of the experimental formulations include 45wt% of microparticles of poly(D,L-lactic-co-glycolic) acid, 55wt% of poly(methyl methacrylate) beads and supplements (10wt-% each) of antibiotics. These formulations provide a selective and excellent control of the local release of antibiotics during a long time period (up to 2 months), avoiding systemic dissemination. The antimicrobial activity of the advanced spacers tested against S. aureus shows that single doses would be enough for the control of the infection. In vitro biocompatibility of cements on human osteoblasts is ensured. This paper is mainly focused on the preparation and characterization of cements and the studies of elution kinetics and bactericidal effects. Developed formulations are proposed as spacers for the treatment of infected arthroplasties, but also, they could be applied in other antibiotic devices to treat relevant bone-related infection diseases.


Acta Biomaterialia | 2017

Photothermal and photodynamic activity of polymeric nanoparticles based on α-tocopheryl succinate-RAFT block copolymers conjugated to IR-780

Raquel Palao-Suay; Francisco Martín-Saavedra; María Rosa Aguilar; Clara Escudero-Duch; Sergio Martín-Saldaña; Francisco J. Parra-Ruiz; Nathan A. Rohner; Susan N. Thomas; Nuria Vilaboa; Julio San Román

The aim of this work was the generation of a multifunctional nanopolymeric system that incorporates IR-780 dye, a near-infrared (NIR) imaging probe that exhibits photothermal and photodynamic properties; and a derivate of α-tocopheryl succinate (α-TOS), a mitochondria-targeted anticancer compound. IR-780 was conjugated to the hydrophilic segment of copolymer PEG-b-polyMTOS, based on poly(ethylene glycol) (PEG) and a methacrylic derivative of α-tocopheryl succinate (MTOS), to generate IR-NP, self-assembled nanoparticles (NPs) in aqueous media which exhibit a hydrophilic shell and a hydrophobic core. During assembly, the hydrophobic core of IR-NP could encapsulate additional IR-780 to generate derived subspecies carrying different amount of probe (IR-NP-eIR). Evaluation of photo-inducible properties of IR-NP and IR-NP-eIR were thoroughly assessed in vitro. Developed nanotheranostic particles showed distinct fluorescence and photothermal behavior after excitation by a laser light emitting at 808nm. Treatment of MDA-MB-453 cells with IR-NP or IR-NP-eIR resulted in an efficient internalization of the IR-780 dye, while subsequent NIR-laser irradiation led to a severe decrease in cell viability. Photocytoxicity conducted by IR-NP, which could not be attributed to the generation of lethal hyperthermia, responded to an increase in the levels of intracellular reactive oxygen species (ROS). Therefore, the fluorescence imaging and inducible phototoxicity capabilities of NPs derived from IR-780-PEG-b-polyMTOS copolymer confer high value to these nanotheranostics tools in clinical cancer research. STATEMENT OF SIGNIFICANCE Multifunctional polymeric nanoparticles (NPs) that combine imaging and therapeutic properties are highly valuable in cancer treatment. In this paper we describe the development of NPs that are fluorescent in the near-infrared (NIR). This is important for their visualization in living tissues that present low absorption and low autofluorescence in this wavelength region (between 700 and 1000nm). Moreover, NPs present photothermal and photodynamic properties when NIR irradiated: the NPs produce an efficient increment of temperature and increase the intracellular reactive oxygen species (ROS) when laser irradiated at 808nm. These tuneable photoinduced properties make the NPs highly cytotoxic after NIR irradiation and provide a new tool for highly precise cancer treatment.


European Journal of Medicinal Chemistry | 2011

Polymeric systems containing dual biologically active ions

Francisco J. Parra-Ruiz; Estefanía Toledano; Mar Fernández-Gutiérrez; Nina Dinjaski; María Auxiliadora Prieto; Blanca Vázquez-Lasa; Julio San Román

This paper reports the synthesis and characterization of dual functional polymerizable salts containing quaternary ammonium cations ionically linked to non steroidal anti-inflammatory drugs (NSAIDs), and their polymers and copolymeric systems obtained with acrylic monomers of different hydrophilicity, e.g. methyl methacrylate and 2-hydroxyethyl methacrylate. NSAIDs used were meclofenamic acid, ketoprofen and ibuprofen. Sustained release of the NSAID from polymeric and copolymeric samples was observed over a period of 10 days and the hydrophobic/hydrophilic character of both the polymeric system and the drug played a role in the release behaviour. The antimicrobial activity of dual functional monomeric and polymeric derivatives was confirmed against Gram-positive and Gram-negative bacteria and polymeric compounds presented higher bactericidal action than the precursory monomers. The extracts of copolymeric samples had anti-inflammatory activity in a nitric oxide inhibitory assay on RAW 264.7 cells and they produced a NO inhibition around 80% within the first seven days.


Polymers & Polymer Composites | 2016

Thermal Crosslinking of Maltodextrin and Citric Acid. Methodology to Control the Polycondensation Reaction under Processing Conditions

M. Castro-Cabado; Francisco J. Parra-Ruiz; A.L. Casado; J. San Román

This paper presents an affordable methodology for the analysis of the crosslinking, by polycondensation reaction, between maltodextrin and citric acid under thermal processing. This methodology is based on three complementary analytical techniques: Fourier Transform Infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and rheometry. FTIR has been found to be a powerful technique for the characterization of both the esterification reaction and other non-covalent interactions between maltodextrin and citric acid. TGA has been mainly applied to quantify the progress of the polycondensation reaction. Rheometry has been extensively used to understand the crosslink formation resulting from the polycondensation process between maltodextrin and citric acid, allowing the determination of the gel time. Furthermore, these techniques have revealed added value when used as complementary techniques. For instance, the FTIR results supported the conclusions from the study of polycondensation reaction progress by TGA. Similarly, the TGA results about the polycondensation reaction temperature are consistent with the rheology study. Overall, the insightfulness and accuracy of the methodology presented in this paper make it very useful as a tool to optimize industrial processing of materials which apply binding systems based on maltodextrin and citric acid.


Journal of Materials Science: Materials in Medicine | 2017

Correction to: Multifunctional decoration of alpha-tocopheryl succinate-based NP for cancer treatment: effect of TPP and LTVSPWY peptide

Raquel Palao-Suay; María Rosa Aguilar; Francisco J. Parra-Ruiz; Sergio Martín-Saldaña; Nathan A. Rohner; Susan N. Thomas; Julio San Román

Every goal I have achieved has been possible in the frame of a large family with complementary skills both personally and professionally. Most of my career has been carried out in the Biomaterials Group of the Institute of Polymer Science and Technology (CSIC) and CIBER-BBN in Spain. I have the honor to work with Prof. Julio San Román from whom I learnt about Polymeric Biomaterials and the generation of scientific knowledge for the development of technologies and products of interest to the Biomedical field. I worked in USA (with Prof. Allan Hoffman), UK (with Prof. Lucy Di Silvio in London and Prof. Andrew Lloyd, Prof. Matteo Santin, and Prof. Sergey Mikhalovsky in Brighton) and France (with Prof. Françoise Ehrburger-Dolle and Dr. Isabelle Morfin). I would like to thank all these investigators and their teams their shared knowledge and opportunities in the past and present. We also collaborate with multiple institutions and researchers of completely different disciplines that enrich and complement our daily investigation, as the multicentric research shown in this article. The present work shows our effort to improve cancer treatments and reduce its side effects through the use of multitargeting nanoparticles. This is one of a series of articles based on amphiphilic copolymers bearing α-tocopheryl succinate as bioactive molecule. The already described good results using this particular technology have generated commercial interest in a pharmaceutical company. A clinical trial to test the effect of similar nanoparticles to avoid cisplatininduced ototoxicity will start in the following months. I would like to strengthen our public-private collaboration to facilitate the transfer of our future know-how in shorter periods of time, working hand-by-hand with specialized companies or maybe creating our own spin-off.


Macromolecular Bioscience | 2016

Enhanced Bioactivity of α‐Tocopheryl Succinate Based Block Copolymer Nanoparticles by Reduced Hydrophobicity

Raquel Palao-Suay; María Rosa Aguilar; Francisco J. Parra-Ruiz; Samarendra Maji; Richard Hoogenboom; Nathan A. Rohner; Susan N. Thomas; Julio San Román

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Julio San Román

Spanish National Research Council

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María Rosa Aguilar

Spanish National Research Council

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Nathan A. Rohner

Georgia Institute of Technology

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Susan N. Thomas

Georgia Institute of Technology

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Sergio Martín-Saldaña

Spanish National Research Council

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J. San Román

Spanish National Research Council

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Juan Parra

Spanish National Research Council

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