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Fornaguera C.,Sagetis Biotech | Solans C.,CSIC - Institute of Advanced Chemistry of Catalonia
Journal of Personalized Medicine | Year: 2017

The design of colloidal nanosystems intended for biomedical applications, specifically in the field of personalized medicine, has increased notably in the last years. Consequently, a variety of characterization techniques devoted to studying nanomedicine interactions with proteins and cells have been developed, since a deep characterization of nanosystems is required before starting preclinical and clinical studies. In this context, this review aims to summarize the main techniques used to assess the interaction of nanomedicines with biological systems, highlighting their advantages and disadvantages. Testing designed nanomaterials with these techniques is required in order to have more information about their behavior on a physiological environment. Moreover, techniques used to study the interaction of nanomedicines with proteins, such as albumin and fibrinogen, are summarized. These interactions are not desired, since they usually are the first signal to the body for the activation of the immune system, which leads to the clearance of the exogenous components. On the other hand, techniques for studying the cell toxicity of nanosystems are also summarized, since this information is required before starting preclinical steps. The translation of knowledge from novel designed nanosystems at a research laboratory scale to real human therapies is usually a limiting or even a final point due to the lack of systematic studies regarding these two aspects: nanoparticle interaction with biological components and nanoparticle cytotoxicity. In conclusion, this review will be a useful support for those scientists aiming to develop nanosystems for nanomedicine purposes. © 2017 by the authors; licensee MDPI, Basel, Switzerland.


Di Mauro P.P.,Sagetis Biotech | Di Mauro P.P.,Ramon Llull University | Gomez-Vallejo V.,CIC Biomagune | Baz Maldonado Z.,CIC Biomagune | And 3 more authors.
Bioconjugate Chemistry | Year: 2015

Drug-loaded nanocarriers and nanoparticulate systems used for drug release require a careful in vivo evaluation in terms of physicochemical and pharmacokinetic properties. Nuclear imaging techniques such as positron emission tomography (PET) are ideal and noninvasive tools to investigate the biodistribution and biological fate of the nanostructures, but the incorporation of a positron emitter is required. Here we describe a novel approach for the 18F-radiolabeling of polyester-based nanoparticles. Our approach relies on the preparation of the radiolabeled active agent 4-[18F]fluorobenzyl-2-bromoacetamide ([18F]FBBA), which is subsequently coupled to block copolymers under mild conditions. The labeled block copolymers are ultimately incorporated as constituent elements of the NPs by using a modified nano coprecipitation method. This strategy has been applied in the current work to the preparation of peptide-functionalized NPs with potential applications in drug delivery. According to the measurements of particle size and zeta potential, the radiolabeling process did not result in a statistically significant alteration of the physicochemical properties of the NPs. Moreover, radiochemical stability studies showed no detachment of the radioactivity from NPs even at 12 h after preparation. The radiolabeled NPs enabled the in vivo quantification of the biodistribution data in rats using a combination of imaging techniques, namely, PET and computerized tomography (CT). Low accumulation of the nanoparticles in the liver and their elimination mainly via urine was found. The different biodistribution pattern obtained for the "free" radiolabeled polymer suggests chemical and radiochemical integrity of the NPs under investigation. The strategy reported here may be applied to any polymeric NPs containing polymers bearing a nucleophile, and hence our novel strategy may find application for the in vivo and noninvasive investigation of a wide range of NPs. (Figure Presented). © 2015 American Chemical Society.


Oh S.,Ramon Llull University | Oh S.,Sagetis Biotech | Wilcox M.,Northumbria University | Pearson J.P.,Northumbria University | And 2 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2015

The objective of this present study was to develop an efficient and simple method, based on the use of a quartz crystal microbalance with dissipation (QCM-D), to evaluate the mucoadhesive characteristics of cationic polymers; chitosan, thiolated chitosan (chitosan-SH), and polyallylamine hydrochloride (PAH), and anionic polymers; hyaluronic acid (HA) and thiolated hyaluronic acid (HA-SH). The experiments were carried out at pH 4 to assess the interaction between mucoadhesive polymers and a mucin-coated gold surface. A key point in the QCM-D protocol development was to evaluate two sources of mucin: native porcine gastric mucin (NPGM) and commercially available porcine gastric mucin (CPGM). QCM-D has shown its potential as a highly sensitive technique that provides information about the interaction of mucoadhesive polymers with gastric mucin. The technique would allow the classification of these polymers in order to further assess their application as base materials for nanocarriers, designed to interact with the mucosal barrier which represents a stumbling block for drug adsorption. © 2015 Elsevier B.V. All rights reserved.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP.2011.1.2-2 | Award Amount: 11.03M | Year: 2012

The objective of the ALEXANDER project is the identification of novel strategies (e.g., proteolytic enzyme strategy, thiomer strategy, zeta potential changing systems, SNEDDS strategy) and the optimization of existing strategies (e.g., disulfide breaking strategy and slippery surface strategy) for the efficient transport of nanocarriers through the mucus gel layer (e.g., intestinal, nasal, ocular, vaginal, buccal, pulmonary). In particular, R&D activities will be focused on the synthesis of functionalized nanocarriers capable of permeating the mucus gel layer and delivering their therapeutic payload to the epithelium. The nanocarriers will be characterized with respect to their physicochemical properties, ability to cross the mucus gel layer, in vitro and in vivo cytotoxicity. The potential of the developed nanocarriers as delivery systems for mucosal administration of macromolecules will be demonstrated via the oral delivery of peptides, oligosaccharides and oligonucleotides and the nasal delivery of a plasmid encoding for an antigen.


PubMed | Sagetis Biotech and University of Innsbruck
Type: | Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | Year: 2016

The objective of this study was to design a novel polyethylene glycol (PEG) derivative exhibiting mucus permeating and mucoadhesive properties. Therefore, the enzymatically degradable phosphate ester, phosphotyrosine (Ptyr) was covalently attached to PEG-diamine. The synthesized PEG-Ptyr was studied in terms of enzymatic degradability on Caco 2 cells and by isolated intestinal alkaline phosphatase (IAP). Furthermore, the influence of enzymatic degradation on charge distribution of the polymer as well as on mucus diffusion and mucoadhesion was investigated. Within this study, the phosphate ester in PEG-Ptyr could be cleaved on the cell monolayer and by the isolated IAP, whereby the degradation rate was 10-fold higher utilizing the isolated enzyme. Implementation of negative charges on PEG due to modification with Ptyr led to an increased electrophoretic mobility, which was reduced after enzymatic degradation of the phosphate ester, most likely due to the alterations in charge distribution on the polymeric backbone. Interactions with mucus components were determined within mucus diffusion studies and rheological investigations. Herein, PEG-Ptyr showed a 3-fold lower mucus diffusion, after incubation with IAP. Within rheological investigations, dynamic viscosities increased by the factor of 3, after the phosphate ester in PEG-Ptyr was degraded by IAP. Results obtained within these experiments provided evidence for the in situ mucoadhesive properties of charge changing phosphorylated polymers. The combination of mucus permeating and mucoadhesive features of phosphorylated PEGs could be a highly interesting tool for future applications, such as for coating nanoparticles.


Di Mauro P.P.,Sagetis Biotech | Borros S.,Sagetis Biotech
Pharmaceutical Research | Year: 2014

Purpose: The objective of this study was to develop a custom-tailored polymeric drug delivery system for paclitaxel, employing a novel biodegradable block co-polymer (P), intended to be intravenously administered, capable of improving therapeutic index of the drug and devoid of the adverse effect of an uncontrolled release.Methods: Paclitaxel loaded nanoparticles (PTX-NPs) were prepared by a modified nanoprecipitation method and emulsification-solvent evaporation method. Our approach involves a focusing on the formulation parameters that can be modified in order to obtain completely customized NPs in terms of size, zeta-potential, drug content and release profile. The biocompatibility and anti-proliferative efficiency of PTX-NPs against glioblastoma cell line were evaluated in vitro by MTS.Results: All formulations showed spherical nanometric (<200 nm), monodisperse (∼0.1), Poly (Ethylene Glycol) (PEG)-coated and negatively charged particles. Selected NPs revealed higher PTX content (up to 24%) in comparison with polyester-based NPs. The release behaviour of PTX from the developed NPs exhibited an approximately first-order profile, without initial burst and characterized by a slow and constant release. Hydrophobic character of the NPs can be set in order to achieve a slower and more controlled release for a prolonged period of time. PTX-NPs were hemocompatible and had significant in vitro anti-tumoral activity against human primary glioblastoma cell line (U-87 MG); cytotoxicity was in time- and drug concentration- dependent manner.Conclusions: The developed drug delivery system proved to be suitable for intravenous administration. NPs characteristics can be customized to obtain high PTX loaded NPs that can improve therapeutic index and avoid an uncontrolled release. © 2014 Springer Science+Business Media New York.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: NMP.2011.2.1-1 | Award Amount: 4.94M | Year: 2012

Ceramic composite materials have for many years been considered to show great promise in the repair of musculoskeletal defects. The materials can mimic the structure of bone, and devices made from the materials can be structured to closely match the mechanical requirements of implant sites. In addition, wide ranges of bioactivity are possible, from inert to fully resorbable. Bioceramics have most commonly been used to date in dentistry, and in some orthopaedic applications, e.g. as an injectable paste for vertebroplasty, or as a coating material for metal orthopaedic implants. However, advances in cellular medicine bring great opportunity for significant growth in the bioceramics industry bioceramics and bioceramic composites offer levels of bioactivity which far exceed those available from metal implants, together with combinations of strength and modulus which exceed anything which can be offered by bioactive polymers on their own. Working in tandem with cells, proteins and other biologically active agents (both from the host and introduced) bioceramic composites have the potential to revolutionise many treatments and therapies, giving new, highly effective early stage clinical interventions for conditions where no approach has existed to date. In order to deliver on the potential shown by bioceramic composites the combination of mechanical design, materials, processing, clinical delivery and subsequent biological interaction all have to be understood in an integrated and systematic way. This proposal will address this underlying research and technological challenge in order to develop new bioceramic products for five SME partner companies.


Patent
Sagetis Biotech | Date: 2013-11-14

The present invention provides polypeptides that cross the blood brain barrier (BBB). These polypeptides are therefore BBB transport agents. The polypeptides are typically able to cross the BBB at a level effective to be therapeutically or diagnostically useful or physiologically significant, either alone or when coupled to a therapeutic or diagnostic agent.


PubMed | Sagetis Biotech and CSIC - Institute of Advanced Chemistry of Catalonia
Type: Journal Article | Journal: Journal of personalized medicine | Year: 2017

The design of colloidal nanosystems intended for biomedical applications, specifically in the field of personalized medicine, has increased notably in the last years. Consequently, a variety of characterization techniques devoted to studying nanomedicine interactions with proteins and cells have been developed, since a deep characterization of nanosystems is required before starting preclinical and clinical studies. In this context, this review aims to summarize the main techniques used to assess the interaction of nanomedicines with biological systems, highlighting their advantages and disadvantages. Testing designed nanomaterials with these techniques is required in order to have more information about their behavior on a physiological environment. Moreover, techniques used to study the interaction of nanomedicines with proteins, such as albumin and fibrinogen, are summarized. These interactions are not desired, since they usually are the first signal to the body for the activation of the immune system, which leads to the clearance of the exogenous components. On the other hand, techniques for studying the cell toxicity of nanosystems are also summarized, since this information is required before starting preclinical steps. The translation of knowledge from novel designed nanosystems at a research laboratory scale to real human therapies is usually a limiting or even a final point due to the lack of systematic studies regarding these two aspects: nanoparticle interaction with biological components and nanoparticle cytotoxicity. In conclusion, this review will be a useful support for those scientists aiming to develop nanosystems for nanomedicine purposes.


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