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<p>Low bioavailability remains a challenge for poorly water-soluble drugs like flutamide, a key therapeutic agent for prostate cancer. To address this, Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) were formulated to enhance solubility, absorption, and therapeutic efficacy. SNEDDS improves drug delivery by forming nanosized emulsions, increasing surface area, and promoting bioavailability. The SNEDDS formulation of flutamide was developed using sesame oil as the oil phase, Tween 20 as the surfactant, and PEG 400 as the co-surfactant. A Design of Experiments (DoE) approach was used to optimize the formulations. The response variables, % CDR (% Cumulative Drug Release) and Self Emulsification Time were considered for systematic DoE optimization. After obtaining the responses, ANOVA was applied for both the responses i.e. self emulsification time studies and % CDR. Then 3 D plots and Contour plots were also plotted using Design Expert Software. Morphological studies were conducted using Transmission Electron Microscopy (TEM), and the particle size, zeta potential, and stability of the formulations were evaluated. Drug release and cytotoxicity were assessed via dialysis and MTT assay on PC-3 prostate cancer cells, respectively. The optimized formulation demonstrated rapid self-emulsification (7.9&#xa0;s) and high %CDR (98.69%). TEM revealed nanoscale uniformity with particle sizes averaging 120.1&#xa0;nm and a zeta potential of -0.0179 mV. FTIR analysis confirmed the stability of functional groups. The IC<sub>50</sub> of the optimized formulation was 177.7 ± 0.05(µg/ml), significantly lower than the pure drug (644.8 ± 0.1405(µg/ml), highlighting its potent cytotoxicity against PC-3 cells. The optimized SNEDDS formulation improved the solubility, stability, and therapeutic efficacy of flutamide. The nanosized formulation facilitated better drug absorption and targeted delivery, enhancing its anticancer potential. The results of the in vitro drug release study were fitted with various kinetics equations like zero order (percent drug release vs. t) and first order (log % drug remaining vs. t) and Higuchi equation to understand the mechanism and kinetics of drug release. R<sup>2</sup> values were calculated for the linear curves obtained by regression analysis of all the plots. Flutamide SNEDDS along with Flavonoid Rutin represent a promising strategy for enhancing bioavailability and therapeutic effectiveness in prostate cancer treatment. Future studies should focus on in vivo pharmacokinetics and safety profiles to confirm clinical applicability.</p> Graphical abstract <p></p>

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Formulation and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the solubility, bioavailability, and anticancer activity of flutamide

  • 期刊论文

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  • 发表日期：

    2026年1月30日

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  • Kavita Sapra,
  • Rupali Sharma,
  • Suman Samaddar,
  • Satish Sardana

摘要

Low bioavailability remains a challenge for poorly water-soluble drugs like flutamide, a key therapeutic agent for prostate cancer. To address this, Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) were formulated to enhance solubility, absorption, and therapeutic efficacy. SNEDDS improves drug delivery by forming nanosized emulsions, increasing surface area, and promoting bioavailability. The SNEDDS formulation of flutamide was developed using sesame oil as the oil phase, Tween 20 as the surfactant, and PEG 400 as the co-surfactant. A Design of Experiments (DoE) approach was used to optimize the formulations. The response variables, % CDR (% Cumulative Drug Release) and Self Emulsification Time were considered for systematic DoE optimization. After obtaining the responses, ANOVA was applied for both the responses i.e. self emulsification time studies and % CDR. Then 3 D plots and Contour plots were also plotted using Design Expert Software. Morphological studies were conducted using Transmission Electron Microscopy (TEM), and the particle size, zeta potential, and stability of the formulations were evaluated. Drug release and cytotoxicity were assessed via dialysis and MTT assay on PC-3 prostate cancer cells, respectively. The optimized formulation demonstrated rapid self-emulsification (7.9 s) and high %CDR (98.69%). TEM revealed nanoscale uniformity with particle sizes averaging 120.1 nm and a zeta potential of -0.0179 mV. FTIR analysis confirmed the stability of functional groups. The IC50 of the optimized formulation was 177.7 ± 0.05(µg/ml), significantly lower than the pure drug (644.8 ± 0.1405(µg/ml), highlighting its potent cytotoxicity against PC-3 cells. The optimized SNEDDS formulation improved the solubility, stability, and therapeutic efficacy of flutamide. The nanosized formulation facilitated better drug absorption and targeted delivery, enhancing its anticancer potential. The results of the in vitro drug release study were fitted with various kinetics equations like zero order (percent drug release vs. t) and first order (log % drug remaining vs. t) and Higuchi equation to understand the mechanism and kinetics of drug release. R2 values were calculated for the linear curves obtained by regression analysis of all the plots. Flutamide SNEDDS along with Flavonoid Rutin represent a promising strategy for enhancing bioavailability and therapeutic effectiveness in prostate cancer treatment. Future studies should focus on in vivo pharmacokinetics and safety profiles to confirm clinical applicability.

Graphical abstract