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Barcelona, Spain

Bonengel S.,University of Innsbruck | Jelkmann M.,University of Innsbruck | Oh S.,Sagetis Biotech | Mahmood A.,University of Innsbruck | And 2 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | 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. © 2016 Elsevier B.V. All rights reserved. Source


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | 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.


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. Source

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