From Poly(Alkyl Cyanoacrylate) to Squalene as Core Material to Design Nanomedicines

International audienceThe discovery of biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles by Patrick Couvreur has opened large perspectives in nanomedicine. Nanoparticles made from different types of PACA monomers have been used in different applications such as the treatment of intracellular infections or the treatment of multidrug resistant hepatocarcinoma. This latest application led to a Phase 3 clinical trial of Livatag ® , a PACA nanoparticulate formulation of doxorubicin. Despite the success of PACA nanoparticles, the need to develop novel type of nanoparticles with higher drug loadings and lower burst release was tackled by the discovery of squalene-based nanoparticles where the drug is covalently linked to the lipid derivative and the resulting conjugate self-assemble into nanoparticles. This pioneering work was accompanied by a wide range of novel applications which mainly dealt with the management of unmet medical needs (e.g., pancreatic cancer, brain ischemia and spinal cord injury). The present Review Article covers the most important steps of the pioneering work of Patrick Couvreur by trying to shed light on his outstanding career that has been a source of inspiration for many decades

Influence of methyl-b-cyclodextrin on the relase kinetics of inulin encapsulated in bioadhesive liposomes

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Dexamethasone palmitate large porous particles: A controlled release formulation for lung delivery of corticosteroids

International audienceWe have optimized a formulation of a prodrug of dexamethasone (DXM), dexamethasone palmitate (DXP) for pulmonary delivery as a dry powder. Formulations were prepared by spray drying DXP with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Hyaluronic Acid (HA) as excipients. Large porous particles around 13 μm were produced with a tap density of 0.05 g/cm 3 and a Fine particle fraction around 40%. The palmitate moiety favors DXP insertion into DPPC bilayers therefore limiting its in vitro release as shown by differential scanning calorimetry. After administering DXP powder intratracheally to rats by insufflation, bronchoalveolar lavage fluid (BALF) and blood samples were collected up to 24 h and DXP and DXM concentrations were determined by HPLC analysis after extraction. PK parameters were evaluated according to a non-compartmental model. We observe that DXP remains for up to 6 h in the epithelial lining fluid (ELF) of the lungs at very high concentration. In addition, DXP concentration decreases according to two characteristic times. Consequently, DXM can be detected at rather important concentration in ELF up to 24 h. The passage of DXP from the lungs to the bloodstream is very poor whereas DXM seems to be absorbed in the blood more easily. These results suggest that once administered DXP undergoes two different processes: hydrolysis into DXM due to the presence of esterases in the lungs and distribution in the lung tissue. This formulation appears promising to reduce systemic exposure and prolong the effect of the drug locally

Pickering emulsions: Preparation processes, key parameters governing their properties and potential for pharmaceutical applications

International audienceAn increased interest in Pickering emulsions has emerged over the last 15 years, mainly related to their very attractive properties compared to regular emulsions, namely their excellent stability and their numerous possible applications. In this review, after detailing the interest of Pickering emulsions, their main preparation processes are presented and their advantages and disadvantages discussed. In the third part, the key parameters that govern Pickering emulsions type, droplet size and stability are analyzed. Finally, the interest and the potential of Pickering emulsions for pharmaceutical applications are exposed and discussed, taking all the administration routes into consideration and focusing on organic particles

pH-sensitive liposomes as a carrier for oligonucleotides: a physico-chemical study of the interaction between DOPE and a 15-mer oligonucleotide in quasi-anhydrous samples

AbstractpH-sensitive liposomes made of dioleoylphosphatidylethanolamine (DOPE)/oleic acid (OA)/cholesterol (CHOL) mixtures were shown to be very promising carriers for oligonucleotides (ON). However, it appeared necessary to clarify the structural consequence of the interactions of ON with the liposome, and especially on DOPE, the lipid responsible for the pH sensitivity. The present study was carried out by differential scanning calorimetry and X-ray diffraction, at low hydration. In such a case, DOPE generally adopt a hexagonal phase. It could be shown that ON increased DOPE transition temperature and increased v/al, as a result of electrostatic interactions between ON and DOPE headgroups. OA was found to have exactly opposite effects, its presence between DOPE molecules inhibiting the formation of hydrogen bonds. The presence of both ON and OA allowed the system to organize in a lamellar phase below the solid/liquid transition, whereas above this temperature ON preferably interacted with DOPE in a hexagonal phase and led OA to separate

Pyrazinoic acid-Poly(malic acid) biodegradable nanoconjugate for efficient intracellular delivery

International audienc