Procédé de préparation de capsules lipidiques fonctionnalisées

The present invention relates to a liquid lipid core/solid lipid shell capsule surface-functionalized with at least one compound containing at least one amino function, characterized in that the lipid core/lipid shell architecture is on the nanometric scale and in that said compound is covalently bonded to said solid lipid shell via a transacylation reaction. It also relates to a method for preparing such capsules

Development of a gemcitabine-polymer conjugate with prolonged cytotoxicity against a pancreatic cancer cell line

Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with limited therapeutic efficacy due to enzymatic hydrolysis by cytidine deaminase (CDA) resulting in compromised half-life in the bloodstream and poor pharmacokinetics. To overcome these limitations, we have developed a methacrylate-based GEM-monomer conjugate, which was polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization with high monomer conversion (∼90%) and low dispersity (<1.4). The resulting GEM-polymer conjugates were found to form well-defined sub-90 nm nanoparticles (NPs) in aqueous suspension. Subsequently, the GEM release was studied at different pH (∼7 and ∼5) with and without the presence of an enzyme, Cathepsin B. The GEM release profiles followed a pseudo zero-order rate and the GEM-polymer conjugate NPs were prone to acidic and enzymatic degradation, following a two-step hydrolysis mechanism. Furthermore, the NPs exhibited significant cytotoxicity in vitro against a model pancreatic cell line. Although, the half-maximal inhibitory concentration (IC50) of the GEM-monomer and -polymer conjugate NPs was higher than free GEM, the conjugates showed superiorly prolonged activity compared to the parent drug

Distribution of lipid nanocapsules in different cochlear cell populations after round window membrane permeation

Hearing loss is a major public health problem, and its treatment with traditional therapy strategies is often unsuccessful due to limited drug access deep in the temporal bone. Multifunctional nanoparticles that are targeted to specified cell populations, biodegradable, traceable in vivo, and equipped with controlled drug/gene release may resolve this problem. We developed lipid core nanocapsules (LNCs) with sizes below 50 nm. The aim of the present study is to evaluate the ability of the LNCs to pass through the round window membrane and reach inner ear targets. FITC was incorporated as a tag for the LNCs and Nile Red was encapsulated inside the oily core to assess the integrity of the LNCs. The capability of LNCs to pass through the round window membrane and the distribution of the LNCs inside the inner ear were evaluated in rats via confocal microscopy in combination with image analysis using ImageJ. After round window membrane administration, LNCs reached the spiral ganglion cells, nerve fibers, and spiral ligament fibrocytes within 30 min. The paracellular pathway was the main approach for LNC penetration of the round window membrane. LNCs can also reach the vestibule, middle ear mucosa, and the adjacent artery. Nuclear localization was detected in the spiral ganglion, though infrequently. These results suggest that LNCs are potential vectors for drug delivery into the spiral ganglion cells, nerve fibers, hair cells, and spiral ligament

Percolation properties of 3-D multiscale pore networks: how connectivity controls soil filtration processes

Quantifying the connectivity of pore networks is a key issue not only for modelling fluid flow and solute transport in porous media but also for assessing the ability of soil ecosystems to filter bacteria, viruses and any type of living microorganisms as well inert particles which pose a contamination risk. Straining is the main mechanical component of filtration processes: it is due to size effects, when a given soil retains a conveyed entity larger than the pores through which it is attempting to pass. We postulate that the range of sizes of entities which can be trapped inside soils has to be associated with the large range of scales involved in natural soil structures and that information on the pore size distribution has to be complemented by information on a critical filtration size (CFS) delimiting the transition between percolating and non percolating regimes in multiscale pore networks. We show that the mass fractal dimensions which are classically used in soil science to quantify scaling laws in observed pore size distributions can also be used to build 3-D multiscale models of pore networks exhibiting such a critical transition. We extend to the 3-D case a new theoretical approach recently developed to address the connectivity of 2-D fractal networks (Bird and Perrier, 2009). Theoretical arguments based on renormalisation functions provide insight into multi-scale connectivity and a first estimation of CFS. Numerical experiments on 3-D prefractal media confirm the qualitative theory. These results open the way towards a new methodology to estimate soil filtration efficiency from the construction of soil structural models to be calibrated on available multiscale data