ABSTRACT

Domperidone (DOM), an antidopaminergic medication, is primarily used as an antiemetic to treat nausea and vomiting caused by a variety of etiologies. It is very insoluble in water and has a poor oral bioavailability of 13-17%. The objective of the current work is to increase domperidone aqueous solubility using nano-structured hydroxy-terminated dendrimers. Dendrimers are distinctive carriers for drug solubilization because of their many special characteristics in terms of size, shape, branching length, and surface functioning. Dendrimers have unique properties that make them potential carriers for many active medicinal compounds due to their structural adaptability. The potential of hydroxy-terminated dendrimers UG1.0, UG2.0, and UG3.0 as solubility enhancers for domperidone was investigated. The effect of concentration and generation of synthesized nano-structured dendritic macromolecules on the solubility of domperidone was studied. The formation of the complexes between domperidone drug molecules and dendrimers was characterized by the FT-IR spectra. The experimental results showed that the solubility of the domperidone was approximately proportional to dendrimer concentration and generation. The water solubility of domperidone has been increased as generation of the hydroxy-terminated dendrimer. Cytotoxicity assay using A-549 lung cancer cell lines and hemolysis results revealed that synthesized dendritic macromolecules are more biocompatible than commercially available polyamidoamine dendrimers (PAMAM).

Keywords: Antiemetic, Cytotoxicity, Dendrimer, Domperidone, Hemolysis, Phase solubility.

ABSTRACT

Prostate 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