Systematic Development of Solid Lipid Nanoparticles of Abiraterone Acetate with Improved Oral Bioavailability and Anticancer Activity for Prostate Carcinoma Treatment

Abstract

In the present work, an attempt was undertaken to improve the oral bioavailability and anticancer activity of abiraterone acetate. Solid lipid nanoparticles (SLNs) were developed using the quality by design (QbD) principles and evaluated through in vitro , ex vivo , and in vivo studies. Solid lipid suitability was evaluated by equilibrium solubility study, while surfactant and cosurfactant were screened based on the ability to form microemulsion with the selected lipid. SLNs were prepared by emulsion/solvent evaporation method using glyceryl monostearate, Tween 80, and Poloxamer 407 as the solid lipid, surfactant, and cosurfactant, respectively. Box-Behnken design was applied for optimization of material attributes and evaluating their impact on particle size, polydispersity index, zeta potential, and entrapment efficiency of the SLNs. In vitro drug release study was evaluated in simulated gastric and intestinal fluids. Cell culture studies on PC-3 cells were performed to evaluate the cytotoxicity of the drug-loaded SLNs in comparison to the free drug suspension. Qualitative uptake was evaluated for Rhodamine B-loaded SLNs and compared with free dye solution. Ex vivo permeability was evaluated on Wistar rat intestine and in vivo pharmacokinetic evaluation on Wistar rats for SLNs and free drug suspension. Concisely, the SLNs showed potential for significant improvement in the biopharmaceutical performance of the selected drug candidate over the existing formulations of abiraterone acetate.

Abiraterone Acetate Loaded Solid Lipid Nanoparticles for Improved Oral Bioavailability: Design of Experiments Based Formulation Optimization, in Vitro, Ex-Vivo and in Vivo Characterization

“…Immediately following collection, the plasma was separated by centrifugation at 5000 rpm for 30 min. The approved UPLC-MS/MS method was used to assess the drug concentration in plasma samples [26].…”

Combined Dopamine and Grape Seed Extract-Loaded Solid Lipid Nanoparticles: Nasal Mucosa Permeation, and Uptake by Olfactory Ensheathing Cells and Neuronal SH-SY5Y Cells

“…Among the above-mentioned carriers, when SLNs are produced, similarly to that occurring also with liposomes, they offer the benefit of loading not only hydrophobic drug substances but also hydrophilic ones, thanks to the presence of a lipid-forming matrix and a polar surfactant stabilizing the resulting nanocarrier, respectively. Additionally, they can also allow sustained release together with safety and efficacy in different pathological conditions [ 8 , 9 , 10 ].…”

Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

“…Many researchers have demonstrated successful loading of various anticancer agents into SLNs and evaluated them against prostate cancer cell lines. Beg et al, 2022, systematically developed SLNs loaded with abiraterone acetate to improve the oral biopharmaceutical properties and for the treatment of prostate cancer. The loading of abiraterone acetate into SLNs have successfully improved the oral bioavailability and anticancer activity against PC-3 cell lines, which was confined by in vitro and in vivo studies [18].…”

“…Beg et al, 2022, systematically developed SLNs loaded with abiraterone acetate to improve the oral biopharmaceutical properties and for the treatment of prostate cancer. The loading of abiraterone acetate into SLNs have successfully improved the oral bioavailability and anticancer activity against PC-3 cell lines, which was confined by in vitro and in vivo studies [18]. Jalilian et al, 2021, developed targeted SLNs for docetaxel with anisamide as ligand to treat prostate cancer.…”