Jigar V Patel

ABSTRACTProstate cancer is an androgen-dependent disease that responds to established therapies that reduce circulating testosterone levels or inhibit androgen binding to the androgen receptor. This has resulted in the development of a variety of new drugs that target this hormone-regulated transcription factor. Oral enzalutamide drug is a potent androgen receptor antagonist inhibitor for the treatment of castration-resistant prostate cancer, but enzalutamide is classified as BCS class II substances with low aqueous solubility. In recent decades, dendrimers have proven to be effective as solubilizers. Due to their special qualities, dendritic macromolecule is an effective drug solubilizing agent. Therefor the current work is to improve the solubility of enzalutamide by using hydroxy-terminated dendritic macromolecules. The potential of nanoscale hydroxy-terminated dendritic macromolecules TG1.0, TG2.0 and TG3.0 as enzalutamide solubility enhancers was investigated. The effect of concentration and generation of synthesized dendritic macromolecules on enzalutamide solubility was investigated. The FT-IR spectra were used to characterize the formation of complexes between drug molecules and dendritic macromolecules. The experimental results revealed that enzalutamide solubility increased with dendrimer concentration and generation. The cytotoxicity and hemolytic potential of synthesized hydroxy-terminated dendritic macromolecules excelled over commercially available polyamidoamine dendrimers (PAMAM) in a cytotoxicity assay using A-549 lung cancer cell lines. Keywords: Enzalutamide, Cytotoxicity, Dendrimer, Hemolysis, Solubility