Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release

Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system

New polymer coating to visualize surgical mesh by MRI

International audienc

Protein-loaded PLGA-PEG-PLGA microspheres: a tool for cell therapy.

International audienceA promising strategy to repair injured organs is possible by delivering a growth factor via poly-(D,L lactide-co-glycolide) (PLGA) microspheres; the latter are coated with adhesion molecules that serve as a support for cell delivery. At present, PLGA is not the optimal choice of polymer because of poor or incomplete protein release. The use of a more hydrophilic PLGA-PEG-PLGA (A-B-A) copolymer increases the degree of protein release. In this work, the impact of different combinations of (B) and (A) segments on the protein-release profile has been investigated. Continuous-release profiles, with no lag phases, were observed. The triblock ABA with a low molecular weight of PEG and a high molecular weight of PLGA showed an interesting release pattern with a small burst (<10% in 48 h) followed by sustained, protein release over 36 days. Incomplete protein release was found to be due to various causes: protein adsorption, protein aggregation and protein denaturation under acidic conditions. Interestingly, cell viability and cell adhesion on microspheres coated with fibronectin highlight the interest of these polymers for tissue engineering applications

New magnetic-resonance-imaging-visible poly(epsilon-caprolactone)-based polyester for biomedical applications

A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(epsilon-caprolactone) (PCL). The substitution degree, calculated by H-1 nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Interaction of gentamicin sulfate with alginate and consequences on the physico-chemical properties of alginate-containing biofilms

BACKGROUND: Alginate is one of the main extracellular polymeric substances (EPS) in biofilms of Cystic Fibrosis (CF) patients suffering from pulmonary infections. Gentamicin sulfate (GS) can strongly bind to alginate resulting in loss of pharmacological activity; however neither the mechanism nor its repercussion is fully understood. In this study, we investigated how GS modifies the alginate macromolecular network and its microenvironment. MATERIAL AND METHODS: Alginate gels of two different compositions (either enriched in guluronate units (G) or enriched in mannuronate units (M)) were crosslinked with Ca and exposed to GS at varying times and concentrations. The complexes formed were characterized via turbidimetry, mechanical tests, swelling assay, calorimetry techniques, nuclear magnetic resonance, Ca displacement, macromolecular probe diffusion and pH alteration. RESULTS: In presence of GS, the alginate network and its environment undergo a tremendous reorganization in terms of gel density, stiffness, diffusion property, presence and state of the water molecules. We noted that the intensity of those alterations is directly dependent on the polysaccharide motif composition (ratio M/G). CONCLUSION: Our results underline the importance of alginate as biofilm component, its pernicious role during antibiotherapy and could represent a potential macromolecular target to improve anti-infectious therapies

New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells

The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair

Permanent Polymer Coating for in vivo MRI Visualization of Tissue Reinforcement Prostheses

The clinical advantage of MRI visualization of prostheses in soft tissue prolapses is very appealing as over 1?000?000 MRI-transparent synthetic meshes are implanted annually, and postoperative complications such as mesh shrinkage and migration are frequent. Here, the synthesis of a new material composed of a DTPA-Gd complex grafted onto a backbone of PMA via a covalent bond is described (DTPA-Gd-PMA). This new polymer is sprayed onto meshes and gives an MR signal for a long period without any significant release of Gd. In vitro cytocompatibility tests on fibroblasts show limited cytotoxicity. Microscopic investigations indicate that vital cells rapidly colonize the material. Finally, coated meshes implanted in rats are easily recognizable using an MR imaging system

Copolymère hydrophobe visible en IRM

The invention relates to a hydrophobic thermoplastic copolymer which is in particular of use for manufacturing and/or coating medical devices, in particular implantable medical devices, characterized in that it is obtained by copolymerization, and in that it comprises at least one first monomer unit and at least one second monomer unit onto which is grafted a paramagnetic-ion-chelating ligand which can complex with such a paramagnetic ion or a paramagnetic-ion-chelating ligand which is complexed with such a paramagnetic ion, wherein the second monomer unit is grafted in sufficient amount for the copolymer to be visible in magnetic resonance imaging when it is complexed with said paramagnetic ion. The invention also relates to a method for obtaining said hydrophobic thermoplastic copolymer