Polymer masked-unmasked protein therapy: Identification of the active species after amylase-activation of dextrin-colistin conjugates.

Polymer masked–unmasked protein therapy (PUMPT) uses conjugation of a biodegradable polymer, such as dextrin, hyaluronic acid, or poly(l-glutamic acid), to mask a protein or peptide’s activity; subsequent locally triggered degradation of the polymer at the target site regenerates bioactivity in a controllable fashion. Although the concept of PUMPT is well established, the relationship between protein unmasking and reinstatement of bioactivity is unclear. Here, we used dextrin–colistin conjugates to study the relationship between the molecular structure (degree of unmasking) and biological activity. Size exclusion chromatography was employed to collect fractions of differentially degraded conjugates and ultraperformance liquid chromatography–mass spectrometry (UPLC–MS) employed to characterize the corresponding structures. Antimicrobial activity was studied using a minimum inhibitory concentration (MIC) assay and confocal laser scanning microscopy of LIVE/DEAD-stained biofilms with COMSTAT analysis. In vitro toxicity of the degraded conjugate was assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. UPLC–MS revealed that the fully “unmasked” dextrin–colistin conjugate composed of colistin bound to at least one linker, whereas larger species were composed of colistin with varying lengths of glucose units attached. Increasing the degree of dextrin modification by succinoylation typically led to a greater number of linkers bound to colistin. Greater antimicrobial and antibiofilm activity were observed for the fully “unmasked” conjugate compared to the partially degraded species (MIC = 0.25 and 2–8 μg/mL, respectively), whereas dextrin conjugation reduced colistin’s in vitro toxicity toward kidney cells, even after complete unmasking. This study highlights the importance of defining the structure–antimicrobial activity relationship for novel antibiotic derivatives and demonstrates the suitability of LC–MS to aid the design of biodegradable polymer–antibiotic conjugates

Development and validation of characterization methods for Lipidots® Multifunctional Platform: a step towards industrial transfer

Lipidots® technology has thrived towards a versatile nanodelivery platform for designing and producing a series of nanoproducts for in vivo diagnostic, in vivo imaging, activated or non-activated targeted drug delivery. In order to ensure quality of final products, characterization as nanotherapeutics is a key parameter. Thus, we are seeking to implement and validate a panel of characterization methods significantly suitable for Lipidots®. More particularly, we have investigated the lipid quantification, the drug/dye encapsulation, release kinetics and leakage to anticipate the nanocarrier behavior in biological media

Observatoire régional du pneumocoque en région Pays de la Loire : résistance de Streptococcus pneumoniae aux antibiotiques en 2007

But de l’étudeEntre le 1er janvier et le 31 décembre 2007, les 20 laboratoires participant à l’observatoire régional du pneumocoque (ORP) Pays de la Loire ont collecté 331 souches invasives de Streptococcus pneumoniae afin d’étudier leur sensibilité aux antibiotiques et la répartition des sérogroupes/sérotypes. Méthode Les concentrations minimales inhibitrices (CMI) de la pénicilline G, de l’amoxicilline et du céfotaxime ont été déterminées par le centre coordinateur, par la méthode de référence de diffusion en milieu gélosé. Les résultats ont été interprétés selon les recommandations du CA-SFM. Les sensibilités à d’autres antibiotiques ont été étudiées et les typages des souches réalisées par le centre coordinateur. Résultats Trois cent trente et une souches ont été isolées en 2007. Elles provenaient de 30 liquides céphalorachidiens, 239 hémocultures, 53 pus d’otites moyennes aiguës et neuf liquides pleuraux. Le pourcentage de pneumocoques de sensibilité diminuée à la pénicilline G (PSDP) était de 39 % et restait plus élevé chez l’enfant (51 %) que chez l’adulte (35 %). Les PSDP étaient souvent multirésistants, avec en particulier un pourcentage élevé de résistance à l’érythromycine (87,6 % contre 8,4 % pour les pneumocoques sensibles à la pénicilline). Enfin, le sérogroupe majoritairement rencontré était le sérogroupe 19 (29,6 % des isolats). Conclusion Une diminution des PSDP a été observée depuis 2001 et les souches de haut niveau de résistance aux β-lactamines restent rares. Le pourcentage de PSDP observés en ORP Pays de la Loire demeure dans la moyenne nationale

Observatoire Régional du Pneumocoque en région Pays de la Loire : résistance de Streptococcus pneumoniae (Sp) aux antibiotiques en 2007

Date du colloque&nbsp;: 12/2008</p

Investigation of selective junctions using a newly developed tunnel current model for solar cell applications

International audienceCarrier transport through a tunnel barrier was modeled and implemented in the numerical device simulator AFORS-HET, which allows calculating the tunnel current between two semiconductor layers or between a metallic contact and a semiconductor layer. Rectangular barriers have been considered, for which an exact quantum solution for the transmission probability can be derived. The implementation in the simulation program was made by approximating the tunnel-interlayer as a “membrane” which modifies the current at the semiconductor/tunnel layer interface, without the need of inserting an additional insulator layer. It is demonstrated that this approximate description of the structure allows to simulate solar cells where tunneling across an insulator plays an important role. The model is then used to investigate new hole collector designs based on a tunnel oxide. It is shown, that the tunnel layer increases the selectivity of the contact for hole extraction, such that very high power conversion efficiencies can be reached