Nanostructures and drug delivery
-
Multi arm PEG-based nanostructures
It has been observed that over 40% of recently discovered therapeutic molecules are insoluble in physiological conditions rendering them either inefficient or toxic. The use of drug delivery nanocarriers enables the safe and efficient spatiotemporal delivery of therapeutic molecules. Despite the breadth of publications on the topic, very few successful polymer-based drug delivery strategies are currently on the market due to the incomplete biocompatibility and/or inefficient drug encapsulation and unstable formulations. Bile acid (BA)-based amphiphilic block copolymers (ABP) provide a promising solution. BAs are natural amphiphilic compounds synthesized in the liver of mammals as emulsifiers in the digestion of fats. Moreover, they contain hydroxyl (OH) groups that can be modified for various applications. The amphiphilicity of polymer-derived BA allows the formation of nanoparticles in aqueous environment enabling the encapsulation of hydrophobic therapeutic molecules in the core of the nanoparticle. Therefore, BAs are excellent candidates as biomaterials due to their non-toxicity, amphiphilic properties, their relative abundance in nature, and the convenience of chemical modifications. Specifically, this project will employ poly(ethylene glycol) (PEG) and poly(allyl glycidyl ether) (PAGE) of various chain lengths synthesized via anionic ring-opening polymerization from the hydroxyl groups of BA to help in the flexibility and stability of the micelles for dual drug and gene delivery directed towards anti-cancer treatment.
-
PLA-based nanocarriers and their structure
The focus of my research is the effect of polymer architecture on the structural properties of polymeric nanoparticles (NP) for drug delivery. We are particularly interested in the effect of the pegylated polyesters polymer architecture on the particle surface properties, internal structure organization and drug encapsulation and release. In order to carry on this objective, libraries of polymers are created using different synthesis strategies and chemistry. NPs are prepared by nanoprecipitation methods or emulsion/solvent removal techniques. The pegylated polymer chains organization and density at the NP surface is investigated by 1H NMR and X-rays photoelectron spectroscopy (XPS). Physical-chemical properties of the NPs, such as resistance to aggregation in saline environment as well as anti-fouling efficacy are also studied in their relationships with PEG surface density and polymer architecture. Protein adsorption resistance is assessed by adsorption isotherms and by microcalorimetry ITC.
-
Development of topical/transdermal formulations made of hybrid nanocarriers
The use of nanocarriers for skin delivery is a promising approach to overcome stratum corneum (SC) barrier and so increase penetration rate of drugs in viable skin layers. However, to date, no evidence was found that nanoparticles themselves are able to translocate into intact viable skin, limiting their possibility to target specific cell populations or systemic circulation. Moreover, although they are determinant for skin penetration, structural properties of nanoparticles in terms of size, surface charge and hydrophilic-lipophilic balance are often underestimated. Our project is aimed at establishing relationships between the physicochemical properties of hybrid lipid-polymer nanoparticles and their interactions with the skin. We hope to optimize a nanocarrier able to penetrate viable skin via follicular pathway without previous SC alteration. For example, such a nanocarrrier could be particularly interesting for transcutaneous vaccination.
