Soutenance de Thèse de Mr Nicolas ROLLEY

The December 2, 2021

Microfluidic formulation of lipid nanocapsules by phase inversion in composition: Mechanistic and phenomenological studies.

Directeur de Thèse: Pr Brice Calvignac

Abstract :

For many years, the continuous production of drug delivery systems assisted by microfluidics has drawn a growing interest because of low batch-to-batch variations, narrow and controlled particle size distributions and easy scale-up. In addition, the high throughput screening of process parameters and the implementation of in situ characterization techniques are some of the possibilities offered by the microfluidics instrumentation. In this context, this thesis work aimed at designing a formulation pilot with its associated microfluidic chips, obtained by Deep Reactive Ion Eatching (DRIE) or 3D printing using Fused Deposition Modeling (FDM). The proof of concept of Galechip (Galenic Lab-on-a-chip) has been carried out through the formulation of nanomedicines, such as lipid nanocapsules (LNC) obtained by a low energy phase inversion composition process. Thereafter, a parametric and systematic study of this formulation process has been investigated with the aim of assessing the formulation conditions that permit to control the size and the polydispersity of the LNC. In this way, the mathematical modeling of these NCL characteristics allowed the establishment of precise formulation maps according to the operating conditions. Finally, the versatility of the equipment has been shown by the implementation of the microfluidic pilot using synchrotron X-ray beams to understand and describe the formulation pathways of LNCs by small angle X-ray scattering (SAXS).

Keywords : EMicrofluidics, 3D Printing, Nanoparticules, Phase Inversion, SAXS