A novel injectable tissue adhesive based on oxidized dextran and chitosan.

Unlabelled: A surgical adhesive that can be used in different surgical situations with or without sutures is a surgeons' dream and yet none has been able to fulfill many such demanding requirements. It was therefore a major challenge to develop an adhesive biomaterial that stops bleeding and bond tissues well, which at the same time is non-toxic, biocompatible and yet biodegradable, economically viable and appealing to the surgeon in terms of the simplicity of application in complex surgical situations. With this aim, we developed an in situ setting adhesive based on biopolymers such as chitosan and dextran.

Tunable delivery of niflumic acid from resorbable embolization microspheres for uterine fibroid embolization.

Uterine arteries embolization (UAE) is a recent technique that aims, by means of particles injected percutaneously, to stifle fibroids (leiomyomas). This treatment is non-invasive, compared with uterine ablation, but generates pelvic pain for a few days. A strategy to reduce the post-embolization pain would be to use calibrated embolization microspheres preloaded with a non-steroidal inflammatory drug (NSAID).

Anti-angiogenic drug delivery from hydrophilic resorbable embolization microspheres: an in vitro study with sunitinib and bevacizumab.

Anti-angiogenic (AA) drugs are proposed as novel agents for targeted therapies in hepatocellular carcinoma (HCC). Loading of AA drugs into drug delivery systems for local delivery would reduce their side effects. The present study investigated the loading and the delivery of two AA drugs, sunitinib and bevacizumab, from one day-resorbable embolization microspheres (REM).

Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization.

Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300-500 μm range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter.

Synthesis of hydrophilic intra-articular microspheres conjugated to ibuprofen and evaluation of anti-inflammatory activity on articular explants.

The main limitation of current microspheres for intra-articular delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is a significant initial burst release, which prevents a long-term drug delivery. In order to get a sustained delivery of NSAIDs without burst, hydrogel degradable microspheres were prepared by co-polymerization of a methacrylic derivative of ibuprofen with oligo(ethylene-glycol) methacrylate and poly(PLGA-PEG) dimethacrylate as degradable crosslinker. Microspheres (40-100 μm) gave a low yield of ibuprofen release in saline buffer (≈2% after 3 months).

Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery.

A novel degradable microsphere (MS) for intra-articular drug delivery, composed of a polyethylene glycol (PEG) core containing degradable regions made of short poly-(lactic-co-glycolic acid) (PLGA) sequences - named PEG-hydrogel MS - was injected into the cavity of sheep shoulder joint, and compared to non-degradable MS devoid of hydrolysable crosslinker in terms of location, degradation and inflammation. One week after intra-articular injection both groups of MS were localized beneath the synovial lining of the synovial fringes located at bottom of the shoulder joint, while a fraction of particles remained in synovial fluid. Histological analyses made one and 4 weeks after intra-articular injection showed cell proliferation around the non-degradable MS entrapped within the synovium.

Elasticity and viscoelasticity of embolization microspheres.

The present study investigates the mechanical properties of three embolization microspheres (E-ms): tris-acryl gelatin microspheres (TG-ms), acrylamido polyvinyl alcohol microspheres (APVA-ms), and polyphosphazene-coated polymethylmethacrylate microspheres (PP-PMMA-ms). Compression and relaxation tests were performed on monolayers of particles and their Young's moduli and relaxation half times (RHTs) were determined. The elasticity of E-ms was evaluated by applying Hertz theory with the assumptions of incompressibility and a Poisson's ratio of 0.

Influence of degradation on inflammatory profile of polyphosphazene coated PMMA and trisacryl gelatin microspheres in a sheep uterine artery embolization model.

Embolization with microspheres is widely applied to treat uterine fibroids. However, the foreign body reaction that could result from the degradation of the microspheres remains to be evaluated to adequately appreciate the tissular tolerance to such biomaterials. We compared herein the in situ degradation of PMMA microspheres coated with polyphosphazene (PMMA-PPms) and trisacryl gelatin microspheres (TGms) and we thoroughly investigated the induced local inflammatory responses, at 1 and 4 weeks after uterine artery embolization in sheep, by using immunohistochemistry and microarray analyses.

Artificial oxygen carrier based on polysaccharides-poly(alkylcyanoacrylates) nanoparticle templates.

Biomimetic nanoparticles based on polysaccharides-poly(alkylcyanoacrylates) copolymers were initially developed in view of drug delivery. Core-shell nanoparticles covered with a sufficiently long brush of polysaccharides were shown to be very low complement activators and have the potential for long circulation times in the bloodstream. Such nanoparticles bearing haemoglobin were envisaged as potential red cell substitutes.

An embolic gelling solution based on acrylic copolymers in ethanol for the treatment of arteriovenous malformations.

We report the preparation of an embolic agent based on specific association of an acrylic copolymer with dedicated particles formulated in ethanol. The copolymers were synthesized by radical polymerization of tertiobutylacrylamide (tBA) and 2-hydroxypropyl methacrylate (HPMA). Influences of the monomers composition, molecular weight and copolymer concentration have been evaluated on an in vitro model.

Recanalization and particle exclusion after embolization of uterine arteries in sheep: a long-term study.

Objective: To compare the long-term evolution of uterine arteries after embolization with the two most commonly used embolic agents for fibroid embolization: nonspherical polyvinyl alcohol (PVA) particles and trisacryl gelatin microspheres (TGMS).

Design: Prospective study.

Setting: University-based interventional radiology, pathology, and reproductive physiology units.

Design aspects of poly(alkylcyanoacrylate) nanoparticles for drug delivery.

Poly(alkylcyanoacrylate) (PACA) nanoparticles were first developed 25 years ago taking advantage of the in vivo degradation potential of the polymer and of its good acceptance by living tissues. Since then, various PACA nanoparticles were designed including nanospheres, oil-containing and water-containing nanocapsules. This made possible the in vivo delivery of many types of drugs including those presenting serious challenging delivery problems.

MR imaging detection of superparamagnetic iron oxide loaded tris-acryl embolization microspheres.

Purpose: To assess by magnetic resonance (MR) imaging the detectability of superparamagnetic iron oxide (SPIO)-labeled microspheres (MSs) in vitro on gelose, ex vivo in kidneys from embolized sheep, and in vivo in kidneys from embolized pigs.

Materials And Methods: With various sizes of SPIO-labeled MSs, common neck and pelvic spin-echo and gradient-echo sequences were acquired on a 1.5-T MR unit.

Enhancing the tolerance of poly(isobutylcyanoacrylate) nanoparticles with a modular surface design.

Polymer nanoparticles are designed as nanovehicles to carry drugs in the body in a controlled manner increasing the concentration of the biologically active substance in the diseased organs and cells. The safety and biocompatibility of these nanosystems are those of the many properties that nanoparticles must meet to be used in vivo. Here we show that the cytotoxicity profile of poly(isobutylcyanoacrylate) (PIBCA) nanoparticles is affected by the way the nanosystems were produced and by the design of their surface.

Bioadhesive properties of poly(alkylcyanoacrylate) nanoparticles coated with polysaccharide.

Development of bioadhesive nanoparticles is of great interest to improve drug absorption through the intestinal barrier. Various Polysaccharide-coated poly(alkylcyanoacrylate) nanoparticles were prepared. The bioadhesive properties of the nanoparticles coated with dextran or chitosan in end-on or side-on conformation were evaluated with an ex-vivo adsorption experiment on rat intestine.

Properties of polysaccharides grafted on nanoparticles investigated by EPR.

The in vivo fate of nanoparticles developed as drug delivery systems is influenced by the surface characteristics of the colloidal particles. In the present work, surface characteristics of a series of poly(isobutylcyanoacrylate) nanoparticles prepared by redox radical emulsion polymerization with polysaccharides of different molecular weight and nature were characterized by EPR. To this aim, a spin label was grafted on the polysaccharide chains after synthesis of the nanoparticles.

Complement activation by core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles: influences of surface morphology, length, and type of polysaccharide.

Purpose: Biodistribution of intravenously administered nanoparticles depends on opsonization. The aim of this study was the evaluation of complement activation induced by nanoparticles coated with different polysaccharides. Influences of size and configuration of dextran, dextran sulfate, or chitosan bound onto nanoparticles were investigated.

Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush.

The aim of this work was to examine the in vitro interactions of core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles (NP) with blood proteins. The particles were prepared by initiating the emulsion polymerization of isobutylcyanoacrylate (IBCA) in the presence of dextran 71 or 15 kDa, heparin, a blend of dextran 71 and heparin, or dextran sulphate in aqueous medium at pH 1. The mechanisms of polymerisation were redox radical (Rad) or anionic (An), resulting in differences in the spatial arrangement of the polysaccharide chains at the NP surface, i.

Heparin coated poly(alkylcyanoacrylate) nanoparticles coupled to hemoglobin: a new oxygen carrier.

A new generation of drug delivery systems based on heparin-poly(isobutylcyanoacrylate) copolymers has been developed to carry hemoglobin. These copolymers spontaneously form, in water, nanoparticles with a ciliated surface of heparin. These nanoparticles maintain the heparin antithrombotic properties and inhibit complement activation.

Novel polysaccharide-decorated poly(isobutyl cyanoacrylate) nanoparticles.

Purpose: The aim of this work was to synthesize new surface-modified nanoparticles using a radical emulsion polymerization of an alkyl cyanoacrylate.

Methods: Isobutyl cyanoacrylate was polymerized in nitric acid 0.2 M containing a polysaccharide (0.

Complement activation by substituted polyacrylamide hydrogels for embolisation and implantation.

An inflammatory reaction has always been observed in vivo around particles used for therapeutic embolisation. Hydrogel microspheres based on Trisacryl, prepared by polymerisation of N-acryloyl-2-amino-2-(hydroxymethyl)-1,3-propanediol in the presence of a crosslinking agent, are amongst the best materials for such a purpose. The aim of this work was to evaluate in vitro the complement-activating capacity of the OH-bearing Trisacryl particles either microporous, or macroporous, or partially substituted with carboxylate, or diethylaminoethyl, or sulphonate groups, in order to be able to decrease the inflammatory reaction in vivo.