Nanostructured formulations of abiraterone and abiraterone acetate: therapeutic potential, pharmacokinetic considerations and bioanalytical perspectives.

Abstract

Abiraterone acetate (AbA) is widely used in the treatment of metastatic castration-resistant prostate cancer. After administration, the prodrug is rapidly converted into its active metabolite, abiraterone (Ab). However, oral administration is compromised by an unfavorable biopharmaceutical profile because the drug has very low solubility in water and absorption which is restricted by dissolution, plus a marked food effect that causes substantial variability in pharmacokinetics. This review examines the therapeutic potential of nanostructured drug delivery systems designed to overcome these drawbacks. Concerning sustained intracellular exposure and co-delivery strategies, polymeric nanoparticles such as those made from PLGA are considered. Lipid-based nanocarriers, including solid lipid nanoparticles and nanostructured lipid carriers, are evaluated with respect to their matrix structure, physicochemical stability, and digestion-dependent behavior that affects intestinal absorption. Nanoamorphous AbA systems are also looked at as a way of improving dissolution, it being necessary to use strict solid-state stabilization in order to prevent recrystallization. Moreover, the review looks at the bioanalytical issues that are relevant to the interpretation of the performance of various formulations, with a focus on LC-MS/MS methods for quantifying AbA, Ab and the related metabolites in biological matrices. The methodological priorities required for clinical translation are identified, among them standardized biorelevant testing and pharmacokinetic study designs that are able to take into account inter-individual variability and food effects. Literature searches were carried out in PubMed and the Web of Science Core Collection, with additional input from ScienceDirect and by screening the reference lists, for publications up to July 2026.