A method to Quantify the Affinity of Cabazitaxel for PLA-PEG Nanoparticles and Investigate the Influence of the Nano-Assembly Structure on the Drug/Particle Association

Purpose: To study the impact of the size and the structure of the nano-assembly on the drug/particle association, determining the intrinsic partition coefficient, in order to better master the encapsulation and release properties of the carrier. Methods: An experimental methodology is proposed to characterize the drug/nanoparticle association by mean of a partition coefficient between the PLA-PEG nanoparticles and the suspending aqueous medium, referred to as K_p. The determination was made from apparent values (referred to as K_p ^ap) measured in the presence of solubilizing agents (albumin and hydroxypropyl-βcyclodextrin) and extrapolation to zero concentration. The structure of nanoparticles was investigated by Transmission Electron Microscopy and static light scattering. Results: Depending on the manufacturing process and the PEG length of the copolymer, the nanoparticles structured either as aggregates of copolymer chains or micelles exhibiting significantly different K_p values. Conclusion: The methodological tool described here showed that the difference in cabazitaxel/nanoparticle association between aggregates and micelles could be attributed to the difference in PLA-PEG chains packing.