Étude de l’influence de différentes méthodes de fabrication sur l’architecture et les propriétés physico-chimiques des nanoparticules à base de PEG-b-PLA
Polymeric nanoparticles can improve the biodistribution and stability of active molecules. Their in vivo performance is closely related to their physicochemical properties, so it is important to study the factors that modify these properties, in order to properly control the nanoparticles performance . The objective of this study is to evaluate the effect of the fabrication method on the properties and surface PEG coverage of nanoparticles. A PEG-b-PLA diblock copolymer, synthesized in our laboratory, was used to prepare nanoparticles through batch nanoprecipitation, flash nanoprecipitation (using an impinging jet micromixer) and microfluidics (using a herringbone micromixer).  We loaded the nanoparticles with three different drugs, having different Log P values, to evaluate the combined effect of Log P and the manufacturing process on the encapsulation efficiency. Size distribution and Zeta Potential were determined by DLS and ELS respectively. The distribution and density of PEG at the surface were quantified by 1H-NMR and the encapsulation efficiency of each drug was determined by HPLC-UV. Size, PdI and surface PEG density of the nanoparticles were found to be strongly affected by the manufacturing process. For its part,  the Zeta Potential is markedly affected by the composition of the medium where the nanoparticles are dispersed. Moreover, the encapsulation efficiency depends mainly on the Log P of the drug, and it is not significantly affected by the fabrication method. The results obtained show the relationship between the preparation method and the characteristics of the nanoparticles, which can help us to select the best method of preparation according to the targeted characteristics and the target tissue.   Keywords: PEG-b-PLA, Polymeric nanoparticles, Batch Nanoprecipitaion, Impinging jet micromixer, Herringbone micromixer, Encapsulation efficiency, Physicochemical properties, Surface PEG, Log P, Injection rate.
PEG-b-PLA Nanoprecipitation flash Log P Polymeric nanoparticles Batch Nanoprecipitaion Impinging jet micromixer Herringbone micromixer Encapsulation efficiency Physicochemical properties Surface PEG Injection rate