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

Abstract

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 Kp. The determination was made from apparent values (referred to as Kp (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 Kp 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.

Keywords: PLA-PEG nanoparticle; drug delivery; partition; release; static light scattering.