Publications

En 10 ans le coût du séquençage d’un génome a été divisé par 10 000. Alors qu’il fallait trois ans pour séquencer le génome humain il ne faut plus que 10 jours avec les séquenceurs de dernière génération. Ces progrès technologiques sur la « lecture » du code génétique ont des répercussions sur de nombreux domaines de la biologie.

Lipid nanocapsules (LNCs) and lipid nanoemulsions (LNEs) are biomimetic synthetic nanocarriers. Their in vitro and in vivo performance was evaluated as a function of their size (25, 50 and 100 nm) and the surface PEG chain length. Analysis methods included complement activation test, particle uptake in macrophage and HEK293(beta 3) cells and biodistribution studies with tumor-grafted mice by fluorescence imaging. A particular attention was paid to keep the concentration of each nanocarrier and to the amount of fluorescent dye in comparable conditions between the in vitro and in vivo studies. Under these conditions, no significant differences were found among the three tested particle sizes and the two nanocarrier types. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable nanocarriers. Passive accumulation of LNCs and LNEs in different tumor types depended on the degree of tumor vascularization.

Synopsis Dermo-pharmacy and cosmetic industries have utilized nanotechnologies for two decades. Initially proposed as vector systems for encapsulation of actives, they gained interest in increasing cutaneous bioavailability. Here, we assay the benefits of self-assembled nanoemulsions bearing ligands for targeting specific skin cells. Nanoemulsions, small droplets ranging typically from 20nm to 150nm, possess key properties for further use in cosmetics: long-term stability, optical transparency, extended range of textures and versatility. We investigated this nanoemulsion system and show ability to encapsulate a range of cosmetic actives with various physicochemical properties. Furthermore, this nanoemulsion presents a low cytotoxicity and is capable of directly targeting skin cells through simple addition of specific ligand in a one-step production protocol. This is of interest for increasing bioavailability of actives encapsulated into nanoemulsion droplets which may have penetrated the skin barrier to specific skin cell. Taken together, these chemical and in vitro observations suggest follow-up with in vivo models. Resume L'utilisation des nanotechnologies en cosmetique et en dermo-pharmacie a commencee il y a vingt ans. Initialement simples vecteurs pour l'encapsulation d'actifs, de nombreux systemes nanoparticulaires ont ete developpes afin d'ameliorer la biodisponibilte cutanee des actifs. Dans notre etude nous proposons un systeme de nanoemulsion pour le ciblage specifique de certaines cellules cutanees, dont les gouttelettes presentent des ligands auto-assembles en surface. Les nanoemulsions, dont la taille des gouttelettes varie entre 20 et 150nm, offrent de nombreux avantages dans leur utilisation en cosmetique: une stabilite prolongee, une transparence optique, une texture modifiable et une polyvalence d'emploi. Nous avons effectivement demontre la possibilite d'utiliser ces nanoemulsions afin d'encapsuler des actifs ayant des proprietes physicochimiques differentes, sans affecter la stabilite du systeme. De plus, ces nanoemulsions presentent une cytotoxicite minime et sont capables de cibler specifiquement certaines cellules cutanees par simple ajout de ligands specifiques lors de leur production en une etape. Ces nanoemulsions offrent un interet majeur dans l'amelioration de la biodisponibilite des actifs encapsules en concentrant les gouttelettes ayant traversees la barriere cutanee sur les cellules cibles. Les caracteristiques physico-chimiques ainsi que les observations in vitro realisees dans cette etude encouragent a tester ces nanoemulsions sur modele in vivo.

Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell–cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution.

Ce travail de thèse concerne l'étude des propriétés physico-chimiques de capsules millimétriques à cœur liquide possédant une membrane fine d'hydrogel d'alginate.
Nous avons dans un premier temps caractérisé le transport de molécules à travers la coque d'hydrogel et estimé le rayon de coupure de cette membrane semi-perméable. De plus, il est possible de limiter la fuite de petits solutés hydrophiles en ajoutant une couche hydrophobe entre le cœur aqueux et la membrane d'alginate. Nous démontrons alors que le temps caractéristique de fuite est déterminé par la géométrie du système (épaisseur de la couche hydrophobe et rayon de la capsule) ainsi que la solubilité et le coefficient de diffusion du soluté dans la phase huileuse.
D'autre part, le gonflement d'une capsule soumise à une différence de pression osmotique nous a permis d'identifier les régimes viscoélastique et viscoplastique de la membrane sous étirement. Nous en déduisons un module élastique de l'hydrogel, qui diminue au-delà du seuil de plasticité. A contrario, lors de la compression de capsules, l'hydrogel est concentré par expulsion irréversible de l'eau, ce qui entraîne une rigidification de sa structure.
Enfin, nous nous sommes intéressés à l'écoulement d'une suspension concentrée de capsules à coeur huileux dans l'eau. Il existe une friction entre les capsules qu'il est possible de contrôler par ajout de tensioactif. Nous avons donc étudié son rôle dans l'écoulement de capsules dans une constriction de type sablier. Ainsi, nous démontrons que le flux est constant et qu'il ne dépend pas de la friction, mais qu'il est fixé par la taille de l'étranglement. En effet, l'écoulement est uniquement déterminé par l'hydrodynamique en phase fluide dans le col du sablier.

Dry skin concerns many individuals, conferring discomfort and even impacting the lives of those severely affected. However, in most cases it can be adequately managed with current moisturizing products.¹

Glycerol is one humectant commonly employed due to its high hygroscopic and hyperosmotic properties. It is used in cosmetics as a moisturizer and in pharmaceutical formulations as an active compound.² Being naturally present in the skin, glycerol was quickly identified for its role in skin hydration, similar to natural moisturizing factors (NMF). A byproduct of triglyceride lipolysis, it is transported from the dermis through keratinocytes by a transmembrane water/glycerol transporting protein, aquaporin 3.^{3, 4}

Glycerol also protects skin against irritant dermatitis and accelerates the recovery of irritated skin.^{5, 6} One in vivo study by Flurh et al.⁷ assumes that the stimulus for barrier repair occurs through water flux due to the hygroscopic properties of glycerol. Likewise, most studies about skin barrier recovery are performed with relatively high concentrations of glycerol, e.g., from 5% to 50%, often dispersed in an emulsion.

The question arises as to whether glycerol acts solely through its hygroscopic properties or implies more specific mechanisms. Indeed, diglycerol and triglycerol, with higher humectant activity, have demonstrated low improvements in skin dryness, compared with glycerol.⁸ Also, one in vivo attempt has been made to characterize the effects of low glycerol doses, e.g. from 1% up to 10%, on water transport through the skin after acute chemical irritation by sodium lauryl sulfate (SLS).⁹ The present article therefore summarizes and clarifies the benefit of glycerol on irritated skin.