Key-roles of phospholipids in anisotropic lipid-based nanoscale dispersions: from self-assembly mechanism and manufacturing process to properties as drug delivery vehicles for IV administration
Prof. Dr. V. Faivre1) – University Paris-Saclay, France
People involved
Dr. François-Xavier Legrand - Paris-Saclay Galien Institute
Dr. Sylviane Lesieur - Paris-Saclay Galien Institute
Yaowei Lu (PhD fellow sponsored by the PRC) - Paris-Saclay Galien Institute
Abstract
There is a growing interest in asymmetry in the field of nanotechnologies for drug delivery. Anisotropy makes it possible to give original properties of mobility, encapsulation or interaction with biological media to the nanoparticles considered.1) The present project focuses on asymmetric particles in their composition to improve the co-encapsulation of compounds for biomedical uses. Since several years, our group has been interested in the development of multicompartmental (Janus) supramolecular organization from amphiphilic derivatives.2) Such particles could be obtained with various raw materials (phospholipids + short-PEG-based surfactants or amphiphilic cyclodextrins) and different preparation processes (for example, hot high-pressure homogenization or nanoprecipitation).
The general objective of this project focused on PEG-based Janus particles is to understand the impact of the phospholipids used on the properties of these anisotropic nanoparticles. Among the physicochemical properties of phospholipids, their transition temperature, the nature of their headgroup, including their charge will be considered. Phospholipid key-roles will be investigated mainly at three levels: formation mechanism, stability, and encapsulation efficiency. To anticipate further use as multidrug delivery systems, formulations showing suitable structure stability will be evaluated as delivery systems through IV administration by performing in-vitro assays to ascertain their compatibility with this route of administration.
Benefit for the community
Regarding nature as a model, phospholipids are well known for playing a key role in compartmentalizing living bodies. In this project, they will be used as building blocks of the newly developed systems to investigate their ability to promote and stabilize anisotropic lipid-based colloids. This should strengthen the place already large (liposomes, lipid nanoparticles for vaccines) of phospholipids in the field of nanotechnologies for drug delivery. By comparing systematically Janus nanoparticles obtained with different lipid materials and different methods, we expect to identify general rules and mechanisms leading to anisotropic nanoparticles. To our opinion, this should help for further development of such fascinating systems with lipids.
Co-encapsulation is a promising approach in drug delivery; for example, it can be considered for the development of fixed-dose combinations, theranostic tools or systems for triggered release. Nevertheless, a prerequisite to ensure the efficacy of such strategies lies in minimizing interactions and/or incorporation competition between the guest substances while preserving the structural integrity of the formulation. One strategy is to conceive nanoscale entities composed of distinct sub-compartments being both tightly juxtaposed and stably delimited to prevent their connectivity. Advantageously, these compartments could be different in composition to adjust their respective hydrophilic-lipophilic behaviors according to the nature of each further co-incorporated drug. In other words, one of the most efficient ways to improve concomitant loadings in a single lipid-based nano-object would be to provide this nano-object with strictly separate compartmented areas by dispersing a two- phase or multiphasic lipid system, each of compartments (or phases) being suitable for optimal solubilization of one of the compounds of interest. This could facilitate independent optimization of their respective encapsulation efficiency. The challenge we want to tackle is to build such devices and to understand how to ensure their interaction while avoiding their merging.
Visit the supervisors lab
Contact to Professor Vincent Faivre.
Development of Janus Particles as Potential Drug Delivery Systems for Diabetes Treatment and Antimicrobial Applications
Pharmaceutics 15, 423
PubMed |
A scalable process to produce lipid-based compartmented Janus nanoparticles with pharmaceutically approved excipients
Nanoscale 10, 3654-3662
PubMed |