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Purpose <p>Breast cancer treatment is often limited by poor drug solubility, low bioavailability, and systemic toxicity associated with conventional chemotherapy. This study aimed to develop and optimize Bosutinib- and Exemestane-co-loaded nanocubosomes (BENCs) to enhance therapeutic efficacy through controlled drug delivery and synergistic anticancer activity.</p> Methods <p>BENCs were formulated using glyceryl monooleate and poloxamer-407 and optimized through a Quality-by-Design (QbD) approach employing a Box–Behnken design. The effects of formulation variables on particle size and entrapment efficiency were investigated. The optimized formulation was characterized for physicochemical properties, drug–excipient compatibility, crystallinity, in vitro drug release, and stability. Anticancer efficacy was evaluated in MCF-7 breast cancer cells through cytotoxicity, cellular uptake, apoptosis, and antioxidant studies.</p> Results <p>The BENCs exhibited a particle size of approximately 297 nm, a polydispersity index of 0.25, a zeta potential of −29 mV, and an entrapment efficiency of 92.50 ± 1.93%. FTIR analysis confirmed the absence of significant drug–excipient interactions, while XRD studies demonstrated the amorphous dispersion of both drugs within the lipid matrix. The formulation provided sustained drug release over 24 h and showed excellent stability under physiological conditions. Cytotoxicity studies revealed a significantly reduced IC₅₀ value (41.62 µg/mL) compared with single-drug treatments. Confocal microscopy confirmed efficient cellular uptake, whereas AO/EtBr staining demonstrated dose-dependent apoptosis. The formulation also exhibited notable antioxidant activity.</p> Conclusion <p>QbD-optimized BENCs demonstrated controlled drug release, high stability, enhanced cellular internalization, and superior anticancer efficacy, highlighting their potential as an effective nanotherapeutic platform for breast cancer treatment.</p> Graphical Abstract <p></p>

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QbD-Driven Development, Physicochemical Characterization, and In Vitro Mechanistic Evaluation of Bosutinib–Exemestane Co-loaded Lipid Cubic Nanoparticles for Enhanced Breast Cancer Therapy

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Priya Singh,
  • Mahaprasad Mohanty,
  • Vemuri Sai Phanindra,
  • Soniya Rani

摘要

Purpose

Breast cancer treatment is often limited by poor drug solubility, low bioavailability, and systemic toxicity associated with conventional chemotherapy. This study aimed to develop and optimize Bosutinib- and Exemestane-co-loaded nanocubosomes (BENCs) to enhance therapeutic efficacy through controlled drug delivery and synergistic anticancer activity.

Methods

BENCs were formulated using glyceryl monooleate and poloxamer-407 and optimized through a Quality-by-Design (QbD) approach employing a Box–Behnken design. The effects of formulation variables on particle size and entrapment efficiency were investigated. The optimized formulation was characterized for physicochemical properties, drug–excipient compatibility, crystallinity, in vitro drug release, and stability. Anticancer efficacy was evaluated in MCF-7 breast cancer cells through cytotoxicity, cellular uptake, apoptosis, and antioxidant studies.

Results

The BENCs exhibited a particle size of approximately 297 nm, a polydispersity index of 0.25, a zeta potential of −29 mV, and an entrapment efficiency of 92.50 ± 1.93%. FTIR analysis confirmed the absence of significant drug–excipient interactions, while XRD studies demonstrated the amorphous dispersion of both drugs within the lipid matrix. The formulation provided sustained drug release over 24 h and showed excellent stability under physiological conditions. Cytotoxicity studies revealed a significantly reduced IC₅₀ value (41.62 µg/mL) compared with single-drug treatments. Confocal microscopy confirmed efficient cellular uptake, whereas AO/EtBr staining demonstrated dose-dependent apoptosis. The formulation also exhibited notable antioxidant activity.

Conclusion

QbD-optimized BENCs demonstrated controlled drug release, high stability, enhanced cellular internalization, and superior anticancer efficacy, highlighting their potential as an effective nanotherapeutic platform for breast cancer treatment.

Graphical Abstract