Critical adverse effects and frequent administration, three times per day, limit the use of flutamide (FLT) as a chemotherapeutic agent in the treatment of prostate cancer. Therefore, our research aimed to develop new cholesterol-based nanovesicles for delivering FLT to malignant cells in an endeavor to maximize its therapeutic efficacy and minimize undesired adverse effects. Draper–Lin small composite design was used to optimize the critical quality attributes of FLT-loaded niosomes and ensure the desired product quality. The influence of the selected four independent variables on mean particle size (Y₁), zeta potential (Y₂), drug entrapment efficiency (Y₃), and the cumulative drug release after 24 h (Y₄) was examined. The optimized nanovesicles were assessed for their in vitro cytotoxicity, ex-vivo absorption via freshly excised rabbit intestine as well as in vivo pharmacokinetics on male rats. TEM confirmed nanovescicles’ spherical shape with bilayer structure. Values of dependent variables were 748.6 nm, −48.60 mV, 72.8% and 72.2% for Y₁, Y₂, Y₃ and Y₄, respectively. The optimized FLT-loaded niosomes exerted high cytotoxic efficacy against human prostate cancer cell line (PC-3) with an IC₅₀ value of 0.64 ± 0.04 µg/mL whilst, it was 1.88 ± 0.16 µg/mL for free FLT. Moreover, the IC₅₀ values on breast cancer cell line (MCF-7) were 0.27 ± 0.07 µg/mL and 4.07 ± 0.74 µg/mL for FLT-loaded niosomes and free FLT, respectively. The permeation of the optimized FLT-loaded niosomes through the rabbit intestine showed an enhancement ratio of about 1.5 times that of the free FLT suspension. In vivo pharmacokinetic study displayed an improvement in oral bioavailability of the optimized niosomal formulation with AUC and C_max values of 741.583 ± 33.557 μg/mL × min and 6.950 ± 0.45 μg/mL compared to 364.536 ± 45.215 μg/mL × min and 2.650 ± 0.55 μg/mL for the oral FLT suspension. With these promising findings, we conclude that encapsulation of FLT in cholesterol-loaded nanovesicles enhanced its anticancer activity and oral bioavailability which endorse its use in the management of prostate cancer.

A key characteristic of prostate cancer (PCa) is the age-correlated rise in 5α-reductase conversion of testosterone to highly active DiHydroTestosterone (DHT). DHT stimulates the uncontrolled growth of prostate gland cells by binding to androgenic receptors. For its management, a variety of treatment approaches have been devised, from surgical treatments to herbal remedies, including chemotherapeutic drugs, which are thought to be the most prevalent form of management. Chemotherapeutic agent administration has demonstrated a number of limitations, chief among them being tissue resistance and non-selectivity, which can be addressed by incorporating the agents into a variety of nanocarriers. Nanotechnology, a fast evolving field, has demonstrated great potential for the creation of innovative medications and diagnostic instruments for a variety of diseases, including cancer. Lipid-based nanoparticles (LNPs), one of the most popular nano-transporters, have several benefits due to their controlled drug release patterns, low toxicity, and excellent compatibility with biological systems. Many medications that are included into LNPs can have their safety, stability, and solubility significantly enhanced. Recent research has used lipid nano-capsules, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and other LNPs. The most popular treatment choices for PCa are discussed in this narrative overview, along with the many lipid nanoparticles and how they were developed. There is also literature-based support for PCa management medications that were successfully incorporated into lipid nanoparticles.