Optimization and evaluation of self-microemulsifying drug delivery systems for enzalutamide and N-desmethyl enzalutamide to enhance antitumor efficacy against prostate cancer

Abstract

Enzalutamide (ENZ) is clinically used primarily for the treatment of advanced prostate cancer. N-desmethyl-enzalutamide (NDE) is a primary and biologically active metabolite of ENZ. However, the poor water solubility and oral absorption of ENZ and NDE limit their clinical applications. To develop ENZ and its active metabolites into new formulations, a self-microemulsifying drug delivery system (SMEDDS) for ENZ and NDE was designed to enhance the solubility and antitumor efficacy of these two drugs during delivery. The results indicated that both ENZ- and NDE-SMEDDS exhibited favorable physicochemical properties and in vitro drug release characteristics. In vivo studies revealed that ENZ- and NDE-SMEDDS had higher AUC and half-lives in comparison with that of ENZ-suspensions (ENZ-sus) and NDE-suspensions (NDE-sus). The SMEDDS demonstrates superior antitumor activity compared to ENZ- and NDE-sus, with NDE-SMEDDS showing slightly better antitumor efficacy than ENZ-SMEDDS. The SMEDDS is a potentially novel oral drug delivery system that can enhance the solubility and antitumor effects of ENZ and NDE. Furthermore, as an active metabolite of ENZ, NDE can be developed into new formulations for antitumor application, offering new strategy for the clinical use of NDE.