Abstract

Prostate carcinoma is the second most leading cause of tumor deaths worldwide and incidence has increasing significantly. In spite of dominant efficacy fosfestrol in treatment of prostate cancer it has hurdles like poor water solubility, low bioavailability and potential side effects on oral administration. The advanced drug delivery approach, cubosomes are reported to show improved oral solubility and bioavailability, and improved anticancer activity. Therefore, the present research was aimed to develop fosfestrol cubosomes to improve solubility, and anticancer efficacy against prostate cancer. Cubosomes were developed by using solvent evaporation technique and optimized using 3² factorial design to verify effect vesicle size and entrapment efficiency using polaxomer-407 as emulsifier and glyceryl monooleate as lipid. The optimized fosfestrol cubosomes were lyophilized using freeze dryer and characterized for morphology by transmission electron microscope, crystallinity by X-ray diffraction, drug release, cytotoxicity, apoptotic potential etc. Optimized fosfestrol cubosomes displayed a mean vesicle size of (183.6±3) nm with polydispersity index 0.248±0.030, zeta potential of -24.6±2.54 mV. Moreover, the percent entrapment efficiency of cubosomes was found to be 94.48 %±4.54 %. Lyophilized fosfestrol cubosomes appeared as unilamellar nano vesicles with somewhat round cubic shapes which displayed maximum release of fosfestrol 93.48 %±3.64 % after 3 h in 0.1 N hydrochloric acid. The fosfestrol cubosomes demonstrated significantly (p<0.01) higher in vitro cytotoxic (low half-maximal inhibitory concentration value (8.30±0.62) µg/ml than plain fosfestrol (22.37±1.82) µg/ml. In addition, flow cytometry results revealed that large proportion of cells were entered in apoptotic stage compared to control and negative control revealing remarkable apoptotic potential of fosfestrol cubosomes. The obtained results revealed the momentous anticancer activity of fosfestrol delivered via cubosomes. Therefore, the developed fosfestrol cubosomes can be used as competent alternative to systemic chemotherapy in effective management of prostate cancer. However; further in vivo animal studies are required to establish its efficacy in the treatment of prostate cancer.