Encapsulation of Vitamin C by Glycerol-Derived Dendrimers, Their Interaction with Biomimetic Models of Stratum corneum and Their Cytotoxicity.

Vitamin C is one of the most sensitive cosmetic active ingredients. To avoid its degradation, its encapsulation into biobased carriers such as dendrimers is one alternative of interest. In this work, we wanted to evaluate the potential of two biobased glycerodendrimer families (GlyceroDendrimers-Poly(AmidoAmine) (GD-PAMAMs) or GlyceroDendrimers-Poly(Propylene Imine) (GD-PPIs)) as a vitamin C carrier for topical application. The higher encapsulation capacity of GD-PAMAM-3 compared to commercial PAMAM-3 and different GD-PPIs, and its absence of cytotoxicity towards dermal cells, make it a good candidate. Investigation of its mechanism of action was done by using two kinds of biomimetic models of stratum corneum (SC), lipid monolayers and liposomes. GD-PAMAM-3 and VitC@GD-PAMAM-3 (GD-PAMAM-3 with encapsulated vitamin C) can both interact with the lipid representatives of the SC lipid matrix, whichever pH is considered. However, only pH 5.0 is suggested to be favorable to release vitamin C into the SC matrix. Their binding to SC-biomimetic liposomes revealed only a slight effect on membrane permeability in accordance with the absence of cytotoxicity but an increase in membrane rigidity, suggesting a reinforcement of the SC barrier property. Globally, our results suggest that the dendrimer GD-PAMAM-3 could be an efficient carrier for cosmetic applications.

ß-Amyloid peptide interactions with biomimetic membranes: A multiparametric characterization.

Alzheimer's disease is the most common form of senile dementia in the world, and amyloid ß peptide1-42 (Aß1-42) is one of its two principal biological hallmarks. While interactome concept was getting forward the scientific community, we proposed that the study of the molecular interactions of amyloid ß peptide with the biological membranes will allow to highlight underlying mechanisms responsive of AD. We have developed two simple liposomal formulations (phosphatidylcholine, cholesterol, phosphatidylglycerol) mimicking neuronal cell membrane (composition, charge, curvature radius). Interactions with Aß1-42 and mutant oG37C, a stable oligomeric form of the peptide, were characterized according to a simple multiparametric procedure based on ThT fluorescence, liposome leakage assay, ATR-FTIR spectroscopy. Kinetic aggregation, membrane damage and peptide conformation provided our first methodologic bases to develop an original model to describe interactions of Aß peptide and lipids.

Microplate assay for lipophilicity determination using intrinsic fluorescence of drugs: Application to a promising anticancer lead, pyridoclax.

Lipophilicity must be necessarily determined in drug discovery since this physicochemical property will directly influence the pharmacokinetics of a drug as its pharmacodynamics profile. Pyridoclax is an original lead, recently identified as very promising in treatment of chemoresistant cancers. The partition coefficient (Kp) of this anticancer drug was determined by microplate assays, well adapted in drug discovery, since being rapid, and requiring only poor drug amounts. The analytical approach was performed either by UV derivative spectrophotometry after validation thanks to a set of basic, neutral and acid reference substances, or originally, by raw fluorescence spectrophotometry by taking advantage of the pyridoclax intrinsic fluorescence. Large unilamellar vesicles (LUVs) were formulated from soybean-, egg-, or dipalmitoyl-phosphatidylcholine, characterized in terms of granulometric properties, ζ potential (determined by DLS), and of phospholipid content (quantified by 1H NMR, also in presence of cholesterol). Whatever the detection method used, log Kp of pyridoclax were in the same magnitude order, and pyridoclax appeared as a lipophilic compound. It was also established that interactions between this lead and biomimetic membranes were influenced by the relative fluidity of the membranes, as confirmed by results of a liposome leakage assay.