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Purpose <p>Poly(lactic‑co‑glycolic acid) (PLGA) nanoparticles are widely used for cancer drug delivery. Co‑encapsulation of agents with complementary mechanisms can improve efficacy at tolerated doses. We evaluated PEGylated PLGA nanoparticles co-loading doxorubicin and capsaicin for activity against breast cancer cells.</p> Methods <p>Nanoparticles were prepared by double emulsion, characterized by size and zeta potential, and assessed for drug loading and release. Cytotoxicity was measured in MCF‑7 cells. In silico work combined molecular docking to the BRCA1 BRCT domain with 100 ns molecular dynamics simulations (MDS) and MM‑GBSA free‑energy analysis to examine complex stability and binding energetics.</p> Results <p>The co‑loaded nanoparticles measured 207 ± 1 nm with an anionic surface (−20.7 mV). Encapsulation efficiencies were 69.65% for doxorubicin and 27.42% for capsaicin in the co‑loaded formulation. Release showed an initial burst followed by sustained diffusion. The co‑loaded nanoparticles reduced MCF‑7 viability more than free drug, with IC₅₀ 3.4 µg/mL versus 5.7 µg/mL for free doxorubicin, and combination index values indicated synergy. Docking predicted favorable binding to BRCA1. MDS showed stable complexes with backbone RMSD ~1.2–1.5 Å, persistent hydrogen bonding, and compact protein geometry. MM‑GBSA gave a favorable overall binding free energy (ΔG_bind = −74.25 ± 5.41 kcal/mol).</p> Conclusion <p>Co‑encapsulation of doxorubicin and capsaicin in PEGylated PLGA nanoparticles yields stable nanostructures with controlled release, synergistic cytotoxicity in MCF‑7 cells, and in silico evidence of stable interaction with the BRCA1 BRCT domain. These data support further preclinical evaluation.</p>

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Co-Delivery of Doxorubicin and Capsaicin Loaded-PEGylated PLGA Nanoparticles to Improve Therapeutic Efficacy against Breast Cancer Cells

  • 期刊论文

  • 发表日期：

    2025年12月3日

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  • Hanan M. Alharbi,
  • Nardeen Z. Alhazmi

摘要

Purpose

Poly(lactic‑co‑glycolic acid) (PLGA) nanoparticles are widely used for cancer drug delivery. Co‑encapsulation of agents with complementary mechanisms can improve efficacy at tolerated doses. We evaluated PEGylated PLGA nanoparticles co-loading doxorubicin and capsaicin for activity against breast cancer cells.

Methods

Nanoparticles were prepared by double emulsion, characterized by size and zeta potential, and assessed for drug loading and release. Cytotoxicity was measured in MCF‑7 cells. In silico work combined molecular docking to the BRCA1 BRCT domain with 100 ns molecular dynamics simulations (MDS) and MM‑GBSA free‑energy analysis to examine complex stability and binding energetics.

Results

The co‑loaded nanoparticles measured 207 ± 1 nm with an anionic surface (−20.7 mV). Encapsulation efficiencies were 69.65% for doxorubicin and 27.42% for capsaicin in the co‑loaded formulation. Release showed an initial burst followed by sustained diffusion. The co‑loaded nanoparticles reduced MCF‑7 viability more than free drug, with IC₅₀ 3.4 µg/mL versus 5.7 µg/mL for free doxorubicin, and combination index values indicated synergy. Docking predicted favorable binding to BRCA1. MDS showed stable complexes with backbone RMSD ~1.2–1.5 Å, persistent hydrogen bonding, and compact protein geometry. MM‑GBSA gave a favorable overall binding free energy (ΔG_bind = −74.25 ± 5.41 kcal/mol).

Conclusion

Co‑encapsulation of doxorubicin and capsaicin in PEGylated PLGA nanoparticles yields stable nanostructures with controlled release, synergistic cytotoxicity in MCF‑7 cells, and in silico evidence of stable interaction with the BRCA1 BRCT domain. These data support further preclinical evaluation.