Lipid nanoparticles as a strategy to enhance abiraterone acetate oral bioavailability: insights into intestinal uptake and pharmacokinetic profiles

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) represent promising nanocarriers for improving the poor oral bioavailability of abiraterone acetate (<10 %), a steroid derivative indicated for the treatment of metastatic prostate cancer. The objectives of this study were twofold: to investigate the mechanisms of intestinal nanoparticle absorption in vitro and to evaluate the in vivo impact of SLN and NLC on the pharmacokinetics and oral bioavailability of abiraterone. SLN and NLC exhibited diameters of respectively 142 and 109 nm, size dispersity of about 0.150 and encapsulation efficiencies around 100 %. In vitro studies demonstrated high internalization of NLC in a monoculture model of Caco-2 cells, as well as in a co-culture of Caco-2:HT29-MTX cells (cultured in a 90:10 ratio) featuring a homogeneous mucus layer. NLC exhibited the ability to efficiently and rapidly (within 1 h of incubation) cross the mucosal barrier to penetrate intestinal cells. After internalization, some NLC appeared to transit through early endosomes, fewer through late endosomes and lysosomes, and a substantial proportion through other intracellular compartments. In vivo , encapsulation of abiraterone resulted in a 125 % increase in oral bioavailability with SLN and a higher 235 % increase with NLC, compared to the free drug suspension administered orally in water. As reported in other studies, significant inter-individual variability in abiraterone absorption was observed, particularly for the free drug. However, this variability was mitigated by encapsulation in lipid nanoparticles, with NLC showing the greatest potential in reducing variability and enhancing bioavailability. • NLC were highly internalized both in Caco-2 cells and Caco-2:HT29-MTX coculture. • NLC crossed the mucosal barrier to penetrate intestinal cells within 1 h incubation. • Encapsulation in NLC increased by 235 % the oral bioavailability of abiraterone. • The absorption variability was mitigated by the encapsulation in lipid nanoparticles.