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Dive into the research topics where Olivier Jordan is active.

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Featured researches published by Olivier Jordan.


European Journal of Pharmaceutics and Biopharmaceutics | 2009

Intra-articular drug delivery systems for the treatment of rheumatic diseases: A review of the factors influencing their performance

Nicoleta Paula Butoescu; Olivier Jordan; Eric Doelker

Osteoarthritis and rheumatoid arthritis are rheumatic diseases for which a curative treatment does not currently exist. Their management is directed towards pain relief achieved with different classes of drugs among which non-steroidal and steroidal anti-inflammatory substances are the most frequently used agents. Nevertheless, the oral or systemic administration of such drugs is hindered by numerous side effects, which could be overcome by their intra-articular (i-a.) administration as dosage forms capable of gradually releasing the active substance. The present review article summarises the research done in the field of drug delivery systems for i-a. injection vs. current management of osteoarthritis or rheumatoid arthritis. Aspects such as the influence of size, shape, polymer matrix or targeted drug on the i-a. retention time, phagocytosis and biological activity will be discussed. Finally, we will comment on the need for adapted delivery systems for the novel and very potent anti-inflammatory drugs, such as inhibitors of the p38 mitogen-activated protein kinase or the IL-1beta conversion enzyme, which to date cannot be properly used due to the severe side effects associated with their systemic administration.


Biomaterials | 2010

The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia

Pol-Edern Le Renard; Olivier Jordan; Antonin Faes; Alke Petri-Fink; Heinrich Hofmann; Daniel A. Rüfenacht; Frederik Bosman; Franz Buchegger; Eric Doelker

We investigated the use of in situ implant formation that incorporates superparamagnetic iron oxide nanoparticles (SPIONs) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. We developed injectable formulations that form gels entrapping magnetic particles into a tumor. We used SPIONs embedded in silica microparticles to favor syringeability and incorporated the highest proportion possible to allow large heating capacities. Hydrogel, single-solvent organogel and cosolvent (low-toxicity hydrophilic solvent) organogel formulations were injected into human cancer tumors xenografted in mice. The thermoreversible hydrogels (poloxamer, chitosan), which accommodated 20% w/v of the magnetic microparticles, proved to be inadequate. Alginate hydrogels, however, incorporated 10% w/v of the magnetic microparticles, and the external gelation led to strong implants localizing to the tumor periphery, whereas internal gelation failed in situ. The organogel formulations, which consisted of precipitating polymers dissolved in single organic solvents, displayed various microstructures. A 8% poly(ethylene-vinyl alcohol) in DMSO containing 40% w/v of magnetic microparticles formed the most suitable implants in terms of tumor casting and heat delivery. Importantly, it is of great clinical interest to develop cosolvent formulations with up to 20% w/v of magnetic microparticles that show reduced toxicity and centered tumor implantation.


Journal of Vascular and Interventional Radiology | 2010

Comparative Study of Chemoembolization Loadable Beads: In vitro Drug Release and Physical Properties of DC Bead and Hepasphere Loaded with Doxorubicin and Irinotecan

Olivier Jordan; Alban Denys; Thierry de Baere; Nathalie Boulens; Eric Doelker

PURPOSE To characterize in vitro the loadability, physical properties, and release of irinotecan and doxorubicin from two commercially available embolization microspheres. MATERIALS AND METHODS DC Bead (500-700 microm) and Hepasphere (400-600 microm) microspheres were loaded with either doxorubicin or irinotecan solutions. Drug amount was quantified with spectrophotometry, bead elasticity was measured under compression, and bead size and loading homogeneity were assessed with microscopy image analysis. Drug release was measured over 1-week periods in saline by using a pharmacopeia flow-through method. RESULTS Almost complete drug loading was obtained for both microsphere types and drugs. Doxorubicin-loaded DC Beads maintained their spherical shape throughout the release. In contrast, Hepaspheres showed less homogeneous doxorubicin loading and, after release, some fractured microspheres. Incomplete doxorubicin release was observed in saline over 1 week (27% +/- 2 for DC beads and 18% +/- 7 for Hepaspheres; P = .013). About 75% of this amount was released within 2.2 hours for both beads. For irinotecan, complete release was obtained for both types of beads, in a sustained manner over 2-3 hours for DC Beads, and in a significantly faster manner as a 7-minute burst for Hepaspheres. CONCLUSIONS The two drug-eluting microspheres could be efficiently loaded with both drugs. Incomplete doxorubicin release was attributed to strong drug-bead ionic interactions. Weaker interactions were observed with irinotecan, which led to faster drug release.


Biomaterials | 2009

Dexamethasone-containing PLGA superparamagnetic microparticles as carriers for the local treatment of arthritis

Nicoleta Paula Butoescu; Christian Alexander Seemayer; Michelangelo Foti; Olivier Jordan; Eric Doelker

Superparamagnetic iron oxide nanoparticles (SPIONs) are attractive materials that have been widely used in medicine for diagnostic imaging and therapeutic applications. In our study, SPIONs and the corticosteroid dexamethasone acetate (DXM) are co-encapsulated into PLGA microparticles for the aim of locally treating inflammatory conditions such as arthritis. The magnetic properties conferred by the SPIONs could help to maintain the microparticles in the joint with an external magnet. The aim of this study was to investigate the interaction between magnetic microparticles and human synovial fibroblasts in terms of microparticle uptake (FACS, confocal and optical microscopy), internalization mechanism (Prussian Blue staining, TEM, immunofluorescence), cell toxicity (MTT) and tissue reaction after intra-articular injection (histology). The results show that the microparticles have an excellent biocompatibility with synoviocytes and that they are internalized through a phagocytic process, as demonstrated by fluorescence-activated cell sorting and morphological analyses of cells exposed to microparticles. Histological analysis showed that the prepared microparticles did not induce any inflammatory reaction in the joint. This type of carrier could represent a suitable magnetically retainable intra-articular drug delivery system for treating joint diseases such as arthritis or osteoarthritis.


European Journal of Pharmaceutics and Biopharmaceutics | 2009

Dexamethasone-containing biodegradable superparamagnetic microparticles for intra-articular administration: physicochemical and magnetic properties, in vitro and in vivo drug release.

Nicoleta Paula Butoescu; Olivier Jordan; Pierre Burdet; Pierre Stadelmann; Alke Petri-Fink; Heinrich Hofmann; Eric Doelker

Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into joints, but still suffer from the drawback of limited retention duration in the articular cavity. In this study, our aim was to prepare and characterize magnetic biodegradable microparticles containing dexamethasone acetate (DXM) for intra-articular administration. The superparamagnetic properties, which result from the encapsulation of superparamagnetic iron oxide nanoparticles (SPIONs), allow for microparticle retention with an external magnetic field, thus possibly reducing their clearance from the joint. Two molecular weights of poly(lactic-co-glycolic acid) (PLGA) were used, 12 and 19 kDa. The prepared batches were similar in size (around 10 microm), inner morphology, surface morphology, charge (neutral) and superparamagnetic behaviour. The SPION distribution in the microparticles assessed by TEM indicates a homogeneous distribution and the absence of aggregation, an important factor for preserving superparamagnetic properties. DXM release profiles were shown to be quite similar in vitro (ca. 6 days) and in vivo, using a mouse dorsal air pouch model (ca. 5 days).


Journal of Controlled Release | 2010

The effects of carrier nature and pH on rhBMP-2-induced ectopic bone formation

Ludmila Luca; Anne-Laure Rougemont; Beat H. Walpoth; Robert Gurny; Olivier Jordan

Carrier nature and pH are important factors for rhBMP-2 osteoinductive activity. As for formulation pH, rhBMP-2 undergoes conformational changes and aggregates when shifting from acidic to neutral pH conditions. The present work investigates, to our knowledge for the first time, the effect of the carrier pH on rhBMP-2 bioactivity in a rat ectopic bone formation model. In addition, the influence of the carrier nature on rhBMP-2 osteoinductive activity was studied by comparing under identical experimental conditions two biopolymers having a very similar chemical structure but opposite charges. Specifically, rhBMP-2 was incorporated into chitosan (CH) and hyaluronan (HY) hydrogels at two different pH values. Hydrogels (0.2 mL) containing rhBMP-2 (150 μg) were injected into quadriceps muscle of Sprague-Dawley rats. Three weeks after injection, animals were euthanized and explanted specimens were analyzed by microcomputerized tomography (micro-CT) and histology. Bone formation was observed in quadriceps muscle with both rhBMP-2-loaded carriers at both pH values. A trend towards higher mineralized bone formation (1.7-fold for CH, 1.4-fold for HY) was observed for rhBMP-2-loaded hydrogels at low pH (4.8 ± 0.2) compared to high pH (6.2 ± 0.2). Significantly higher (two- to three-fold) mineralized bone formation was observed with rhBMP-2/HY hydrogel compared to rhBMP-2/CH hydrogel, although bone was more mature with the CH hydrogel. These results indicate that both hydrogels are effective carriers for rhBMP-2 and that the carrier nature influences bone formation in terms of volume and quality. This study also provided evidence that the formulation pH is a very important factor that may be critical to design efficient carriers for BMP-2.


European Journal of Pharmaceutics and Biopharmaceutics | 2015

Chitosan as a starting material for wound healing applications

Viorica Patrulea; Vasile Ostafe; Gerrit Borchard; Olivier Jordan

Chitosan and its derivatives have attracted great attention due to their properties beneficial for application to wound healing. The main focus of the present review is to summarize studies involving chitosan and its derivatives, especially N,N,N-trimethyl-chitosan (TMC), N,O-carboxymethyl-chitosan (CMC) and O-carboxymethyl-N,N,N-trimethyl-chitosan (CMTMC), used to accelerate wound healing. Moreover, formulation strategies for chitosan and its derivatives, as well as their in vitro, in vivo and clinical applications in wound healing are described.


Journal of Biomedical Materials Research Part A | 2011

Injectable rhBMP‐2‐loaded chitosan hydrogel composite: Osteoinduction at ectopic site and in segmental long bone defect

Ludmila Luca; Anne-Laure Rougemont; Beat H. Walpoth; Ludovic Boure; Andrea Tami; James M. Anderson; Olivier Jordan; Robert Gurny

Carriers for bone morphogenetic protein-2 (BMP-2) used in clinical practice still suffer from limitations such as insufficient protein retention. In addition, there is a clinical need for injectable carriers. The main objective of this study was to assess bone forming ability of rhBMP-2 combined either with chitosan hydrogel (rhBMP-2/CH) or chitosan hydrogel containing β-tricalcium phosphate (β-TCP) (rhBMP-2/CH/TCP). Formulations were first compared in a rat ectopic intramuscular bone formation model, and the optimal formulation was further evaluated in healing of 15-mm critical size defect in the radius of a rabbit. Three weeks after injection ectopically formed bone was analyzed by microcomputerized tomography (micro-CT) and histology. Significantly higher (4.7-fold) mineralized bone formation was observed in the rhBMP-2/CH/TCP group compared to rhBMP-2/CH group. In a pilot study, defect in a rabbit radius treated with rhBMP-2/CH/TCP showed incomplete regeneration at 8 weeks with composite leakage from the defect, indicating the need for formulation refinement when segmental defect repair is foreseen.


Carbohydrate Polymers | 2012

In vitro evaluation of an RGD-functionalized chitosan derivative for enhanced cell adhesion

Annasara Hansson; Nour Hashom; Françoise Falson; Patricia Rousselle; Olivier Jordan; Gerrit Borchard

Tissue repair is a spontaneous process that is initiated on wounding. However, if this complex mechanism is impaired or not sufficient the use of biomaterials might increase the chance of successful healing. In this view, an RGD-functionalized polymer was developed to promote dermal healing. A water-soluble chitosan derivative, carboxymethyl-trimethylchitosan (CM-TM-chitosan) was synthesized and GRGDS-moieties were grafted to the backbone at a concentration of 59 nmol/mg polymer to increase cell-biomaterial interaction. Tested in vitro with cultured human dermal fibroblasts, the developed polymer showed good biocompatibility and the initial adhesion was increased by 3-5 times due to the GRGDS-moieties. Moreover, cell spreading was specific to the interaction with GRGDS, giving a 12-fold increase of cells showing a fully spread morphology within 30 min. Overall, CM-TM-chitosan conjugated with GRGDS-peptides may prove useful as a biomaterial in wound healing.


Journal of Biomedical Materials Research Part A | 2009

Novel thermosensitive chitosan hydrogels: In vivo evaluation

Emilie Patois; Suzanne Osorio-da Cruz; Jean-Christophe Tille; Beat H. Walpoth; Robert Gurny; Olivier Jordan

Chitosan is an attractive biopolymer for the preparation of hydrogels. Its unique combination of biocompatibility, biodegradability, bioadhesivity, and tissue-promoting abilities allows pharmaceutical applications. We investigated novel thermosensitive hydrogels based on chitosan homogeneously reacetylated to a deacetylation degree of about 50%, combined with selected polyols or polyoses such as trehalose, a nontoxic polysaccharide. The latter, a gel-inducing and lyoprotective agent enabled the formulation to be lyophilized and rehydrated without affecting the thermosensitive behavior. This made possible long-term storage and promoted its use in a clinical setup. The thermally induced sol-gel transition allowed injectability and in situ setting. Rheological characterization revealed that storage moduli could be increased by one decade by increasing the chitosan concentration from 1.4 to 2.2% (w/w). Evaluation in vivo provided evidence of in situ implant formation in subcutaneous tissue of Sprague-Dawley rats and permanence for up to 3 months. Histopathological analysis demonstrated a mild, chronic, inflammatory reaction that disappeared with the complete absorption of the gel implant over a few months period. Such in situ forming hydrogels could be advantageous for specific applications in drug delivery and tissue engineering.

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Alban Denys

University of Lausanne

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Pierre Bize

University of Aberdeen

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