Evaluation of the surface properties of dextran-coated poly(isobutylcyanoacrylate) nanoparticles by spin-labelling coupled with electron resonance spectroscopy

International audienc

Drug delivery to resistant tumors: the potential of poly(alkyl cyanoacrylate) nanoparticles

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

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A NEW GENERATION OF POLYMER NANOPARTICLES FOR DRUG DELIVERY

International audienceOne of the main interests of using polymer nanoparticles as drug carrier systems is to control the delivery of the drugs including their biodistribution. During the last decade, it was clearly demonstrated that surface properties of nanoparticles were the key factor which determined the in vivo fate of such a carrier. Thus, the purpose of this work was to develop a new method which allows the easy fabrication of nanoparticles with versatile surface properties using polysaccharides. This preparation was based on the use of a redox radical polymerization reaction applied for the first time to the emulsion polymerization of alkylcyanoacrylates in aqueous continuous media. The dispersion of nanoparticles was very stable. The nanoparticle surfaces were coated with polysaccharides and their characteristics can be modulated by the type and the molecular weight of the polysaccharides used during the synthesis. Interestingly the biological properties of the polysaccharide immobilized on the nanoparticle surface can be preserved opening very interesting perspectives for such nanoparticles. This method also offers a new strategy for the design of modular biomimetic nanoparticles as drug carrier systems with multiple functions. One of the applications considered in this work was to use these nanoparticles coupled with haemoglobin as an oxygen carrier

Formulation of stable detoxifying w/o/w reactive multiple emulsions: in vitro evaluation

International audienceOver the last decade, acute drug intoxications have been known to be a serious threat to the public health field. Nevertheless, only a few means of imperfect detoxication treatments have, unfortunately, been applied to date. This paper presents water-in-oil-in-water (w/o/w) reactive multiple emulsions (ME) as an efficient method of in vitro detoxication against Nivaquine, a drug widely accused of being used in suicide attempts. The detoxication efficiency of these emulsions is attributed to the use of an adequate extractant-trapping agent couple giving a good extraction yield. Interestingly, some prepared emulsions showed a Nivaquine extraction yield of about 85%. A series of studies was conducted to recognize the effect of the preparation protocol, the emulsion ingredients, especially the extractant-trapping agent couple, and the experimental conditions on the extraction output. The extraction yield increases with the concentration of the extractant and with the alcalinization of the extraction medium. Globally, these reactive multiple emulsions have shown to be stable and highly detoxifying against Nivaquine taken as a toxic molecule model. Moreover, the process of Nivaquine extraction by the extractant in the oily phase and its trapping in the internal aqueous phase has been elucidated and validated

Erythrocyte-Inspired Discoidal Polymeric Nanoconstructs Carrying Tissue Plasminogen Activator for the Enhanced Lysis of Blood Clots

Tissue plasminogen activator (tPA) is the sole approved therapeutic molecule for the treatment of acute ischemic stroke. Yet, only a small percentage of patients could benefit from this life-saving treatment because of medical contraindications and severe side effects, including brain hemorrhage, associated with delayed administration. Here, a nano therapeutic agent is realized by directly associating the clinical formulation of tPA to the porous structure of soft discoidal polymeric nanoconstructs (tPA-DPNs). The porous matrix of DPNs protects tPA from rapid degradation, allowing tPA-DPNs to preserve over 70% of the tPA original activity after 3 h of exposure to serum proteins. Under dynamic conditions, tPA-DPNs dissolve clots more efficiently than free tPA, as demonstrated in a microfluidic chip where clots are formed mimicking in vivo conditions. At 60 min post-treatment initiation, the clot area reduces by half (57 ± 8%) with tPA-DPNs, whereas a similar result (56 ± 21%) is obtained only after 90 min for free tPA. In murine mesentery venules, the intravenous administration of 2.5 mg/kg of tPA-DPNs resolves almost 90% of the blood clots, whereas a similar dose of free tPA successfully recanalizes only about 40% of the treated vessels. At about 1/10 of the clinical dose (1.0 mg/kg), tPA-DPNs still effectively dissolve 70% of the clots, whereas free tPA works efficiently only on 16% of the vessels. In vivo, discoidal tPA-DPNs outperform the lytic activity of 200 nm spherical tPA-coated nanoconstructs in terms of both percentage of successful recanalization events and clot area reduction. The conjugation of tPA with preserved lytic activity, the deformability and blood circulating time of DPNs together with the faster blood clot dissolution would make tPA-DPNs a promising nanotool for enhancing both potency and safety of thrombolytic therapies.