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Purpose <p>The present study aimed to develop a darolutamide (DRM) loaded PEGylated DRM liposomes (DRML) to improve pharmacokinetics in the treatment of prostate cancer.</p> Methods <p>A 3<sup>2</sup> full factorial design was employed to evaluate the influence of Hydrogenated Soy Phosphatidylcholine (HSPC) and cholesterol concentrations on key formulation parameters, including particle size and entrapment efficiency (EE). The optimized PEGylated DRM liposomal formulation (DRML-9) was further characterized by transmission electron microscopy (TEM) for morphology, X-ray diffraction (XRD) for crystallinity, and differential scanning calorimetry (DSC) for thermal behavior.</p> Results <p>Among 13 liquid formulations (PDL–1 to PDL–13), PDL–9, comprising 15 mg HSPC, 35mg cholesterol, exhibited optimal characteristics, including particle size (87.8 ± 3.25) and higher entrapment (95.57 ± 1.67%). Fourier Transform Infrared spectroscopy (FTIR) spectra confirmed drug-excipient compatibility, and Differential Scanning calorimetry (DSC) as well as X-Ray Diffraction Analysis (XRD) data indicated the amorphization and molecular dispersion of DRM in the liposomal formulation. The DRML-9 formulation exhibited superior drug release (71.56 ± 3.48%) at tumor pH compared to blood pH (16.35 ± 1.17%). DRML-9 significantly inhibited LNCaP prostate cancer cell proliferation (<i>P</i> &lt; 0.001) and induced apoptosis as evidenced by Annexin-V/PI staining. Cell cycle study in DRML resulted in almost 2-fold increase in S-phase arrest compared to DRM alone. Pharmacokinetic evaluation demonstrated a 3.6-fold increase in AUC₀–t and AUC₀–∞ of DRML-9 over pure DRM.</p> Conclusion <p>Collectively, these findings establish DRML-9 as a promising intravenous delivery platform for improving the therapeutic potential of DRM in treatment of prostate cancer.</p> Graphical Abstract <p></p>

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Development and Optimization of PEGylated Darolutamide-Loaded Liposomes for Treatment of Prostate Cancer: in Vitro and in-vivo Characterization

  • 期刊论文

  • 发表日期：

    2026年2月13日

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  • Vinod Patil,
  • Harshal Pawar

摘要

Purpose

The present study aimed to develop a darolutamide (DRM) loaded PEGylated DRM liposomes (DRML) to improve pharmacokinetics in the treatment of prostate cancer.

Methods

A 32 full factorial design was employed to evaluate the influence of Hydrogenated Soy Phosphatidylcholine (HSPC) and cholesterol concentrations on key formulation parameters, including particle size and entrapment efficiency (EE). The optimized PEGylated DRM liposomal formulation (DRML-9) was further characterized by transmission electron microscopy (TEM) for morphology, X-ray diffraction (XRD) for crystallinity, and differential scanning calorimetry (DSC) for thermal behavior.

Results

Among 13 liquid formulations (PDL–1 to PDL–13), PDL–9, comprising 15 mg HSPC, 35mg cholesterol, exhibited optimal characteristics, including particle size (87.8 ± 3.25) and higher entrapment (95.57 ± 1.67%). Fourier Transform Infrared spectroscopy (FTIR) spectra confirmed drug-excipient compatibility, and Differential Scanning calorimetry (DSC) as well as X-Ray Diffraction Analysis (XRD) data indicated the amorphization and molecular dispersion of DRM in the liposomal formulation. The DRML-9 formulation exhibited superior drug release (71.56 ± 3.48%) at tumor pH compared to blood pH (16.35 ± 1.17%). DRML-9 significantly inhibited LNCaP prostate cancer cell proliferation (P < 0.001) and induced apoptosis as evidenced by Annexin-V/PI staining. Cell cycle study in DRML resulted in almost 2-fold increase in S-phase arrest compared to DRM alone. Pharmacokinetic evaluation demonstrated a 3.6-fold increase in AUC₀–t and AUC₀–∞ of DRML-9 over pure DRM.

Conclusion

Collectively, these findings establish DRML-9 as a promising intravenous delivery platform for improving the therapeutic potential of DRM in treatment of prostate cancer.

Graphical Abstract