After antibiotics administration, a fraction of the drug is not absorbed and follows its progression to the colon before elimination. Intestinal excretion of residual and active antibiotics has various deleterious consequences: Intestinal flora disturbance and perturbation of the resistance functions to exogenous bacteria colonisation, Selection of resistant micro-organisms to administered antibiotics, whose dissemination can constitute a resistance mechanisms source, in a context of multiresistance development of various human pathogenic species. Accidental or deliberate ingestion of medicines or domestic substances also represents a situation where adsorption or inactivation of undesirable molecules in the digestive tract is crucial. Therefore, there is a real need for new galenic forms allowing elimination by adsorption or inactivation of undesirable molecules in the gastrointestinal tract, and overcoming disadvantages and obstacles of existing forms. The present invention relates to galenic formulations including particles capable of specifically adsorbing undesirable molecules in the digestive tract, these particles comprising a cationic polymer associated to a metallic ion. The invention also relates to the particles preparation process and use. The formulations described in the invention can be administered in all oral forms, including capsules and are designed to specifically release the adsorbents at a specific site of the intestinal tract (small intestine, colon). The formulations can be administered before, during or after administration of an antibiotic.
Despite the ongoing debate about the safety of nanomedicines and especially the wide interest raised by their lung administration for the treatment of various diseases, little information is available on their effect towards the airway epithelial barrier function. We carry out study to evaluate the damages induced to the pulmonary epithelium upon exposure to biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs). For this purpose we have used an in vitro model of Calu-3 cell to mimic the bronchial epithelial barrier. Positively and negatively charged as well as neutral PLGA NPs were obtained by coating their surface with chitosan (CS), poloxamer (PF68) or poly(vinyl alcohol) (PVA), respectively. The role of NP surface chemistry and charge on the epithelial resistance and mucus turnover was investigated. MUC5AC was used as a marker of mucus production. It was shown that the interaction with mucin reduced the penetration of CS- and PVA-coated NPs while the hydrophilic PF68-coated NPs were able to diffuse across the mucus barrier leading to a higher intracellular accumulation. NPs did not interfere with the formation and maintenance of tight junctions, with the exception of CS-coated NPs which caused a transient but reversible decrease of the trans-epithelial electrical resistance (TEER). NPs did not increase the MUC5AC mRNA expression or the protein levels regardless of their surface properties. Moreover, non inflammation was observed as evaluated by measurement of proinflammatory cytokines. These in vitro results highlight that biodegradable PLGA NPs may not harm the integrity and function of the bronchial airway barrier and demonstrate the crucial role of NPs surface properties to achieve a controlled and sustained delivery of drugs via the pulmonary route. To know more paper 1 and paper 2
Together with our colleagues from irsn, we have developed a nanoemulsion containing calixarene molecule, a selective chelating agent for actinides such as uranium, as specific emergency treatments in case of contamination through wound, intact skin or hair after accidental or malevolent spread of this toxic radionuclide. An oil-in-water nanoemulsion composed of paraffin or mineral oil, water and surfactants was produced and its ability to prevent uranium ion diffusion through the skin was evaluated by permeation studies using pig ear skin biopsies excoriated by tape-stripping as an injured skin model. Nanoemulsion characterisation suggests that calixarene molecules are localised at the surface of oily droplets sizing around 150 nm in the nanoemulsion, therefore favourable for uranium extraction from an aqueous phase. Ex vivo studies results showed that calixarene nanoemulsion trap and prevent uranium diffusion through the skin, compared with no treatment. These preliminary results obtained ex vivo need to be confirmed by further studies in vivo, but both calixarene formulations can be regarded as promising treatments for cutaneous contaminations by uranium soluble compounds.
Patent - Paper 1 – Paper 2 – Paper 3
We have introduced in lipoplexes a Hyaluronic acid-phospholipid conjugate. The modified lipoplexes were able to target specifically MDA-MB 231 cells expressing CD44 receptor. Transfection was blocked by antiCD44 antibody. This system open up interesting properties in the design of targeted delivery of DNA to cancer cells.
We have designed Pectin beads containing -lactamases for the hydrolysis of colonic residual antibiotics responsible for the emergence of resistance. In previous experiments, beads were shown to increase the level of active beta lactamases in the feces. We now show that release occurs only in the colon since no modification of the pharmacokinetics was shown in rat following simultaneous administration of beads containing the enzyme and amoxicillin Abstract and more…