Abstract

Background: Flutamide (FLT) is a non steroidal antiandrogenic drug used to treat prostate cancer. Its poor aqueous solubility and toxicity are the major hindrance for oral drug delivery. The aims of this study are to introduce nanoformulation of flutamide to increase its aqueous solubility thereby improves the therapeutic efficacy of the chemodrug.

Methods: Poly (vinyl alcohol) (PVA) coated flutamide nanoparticles (PVA FLT NPs) were formulated by nanoprecipitation method and characterized by DLS, TEM, FTIR, Drug release profile and biological assays.

Results: The PVA FLT nanoparticles were about 300nm size and spherical in shape. The PVA coated flutamide nanoparticles were monodispersed and polycrystalline. The FTIR spectra confirmed the encapsulation of flutamide in PVA FLT NPs. The encapsulation efficiency and loading efficiency was found to be about 78% and 15% respectively. The in vitro drug release of nanoparticles was calculated and it showed a sustained release up to 120 hrs at pH 7.4. The in vitro cytotoxicity, colony forming ability and blood compatibility were also investigated. The in vitro cytotoxicity study indicated the dose dependent cytotoxicity of PVA FLT NPs. In vitro clonogenic assay revealed that the PVA FLT NPs treated PC3 cells had less colony forming ability than the untreated PC3 cells. In vitro hemolysis assay and blood aggregation studies confirmed the hemocompatibility of the prepared PVA FLT NPs.

Conclusion: We reported PVA coated FLT NPs were prepared by nanoprecipitation were more aqueous soluble than FLT, which increased its therapeutic efficacy for prostate cancer cells.

Keywords: Cytotoxicity, flutamide, poly (vinyl alcohol), nanoparticles, prostate cancer, therapy.

Graphical Abstract