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<p>Gemcitabine (GCN) is a chemotherapy agent effective against breast cancer (BC), as it inhibits cell proliferation by blocking DNA synthesis. However, GCN’s short half-life and hydrophilic nature limit its bioavailability and effectiveness. This study aimed to enhance the targeting, efficacy, sustainability, and penetration of GCN for BC treatment by developing a nasal spray containing GCN-loaded liposomes (GLDL). The Box-Behnken design was employed to optimize various formulations of GLDL. The efficacy of the optimized GLDL formulation was assessed using an experimental rat model treated with 7,12-dimethylbenz(a)anthracene (DMBA). The optimized GLDL formulation consisted of 3.25% phospholipid, 15% propylene glycol, and 10% ethanol. This optimized GLDL formulation demonstrated a 55.15% reduction in GCN release, a 4.67-fold enhancement in GCN permeation, and a 4.4-fold enhancement in GCN bioavailability over a 24-h period compared to free GCN. When compared to the DMBA-positive group, the nasal GLDL formulation resulted in a remarkable 97.65% reduction in tumor volume. The optimized GLDL exhibited antiproliferative properties, as demonstrated by histopathological analysis of the formulation. Furthermore, there was a notable 15.83-fold increase in the tumor accumulation of GCN in the nasal GLDL group compared to the oral GCN group. Importantly, the nasal GLDL formulation did not adversely affect erythropoiesis, immune function, or liver and kidney functions. The nasal GLDL spray is anticipated to be a promising and effective treatment option for BC.</p>

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Liposomes-enabled gemcitabine therapy for breast cancer: in vitro and in vivo studies

  • 期刊论文

  • 发表日期：

    2026年7月23日

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  • Ali Al-Shammari,
  • Amani M. El Sisi,
  • Amr Gamal Fouad,
  • Shahira F. El-Menshawe

摘要

Gemcitabine (GCN) is a chemotherapy agent effective against breast cancer (BC), as it inhibits cell proliferation by blocking DNA synthesis. However, GCN’s short half-life and hydrophilic nature limit its bioavailability and effectiveness. This study aimed to enhance the targeting, efficacy, sustainability, and penetration of GCN for BC treatment by developing a nasal spray containing GCN-loaded liposomes (GLDL). The Box-Behnken design was employed to optimize various formulations of GLDL. The efficacy of the optimized GLDL formulation was assessed using an experimental rat model treated with 7,12-dimethylbenz(a)anthracene (DMBA). The optimized GLDL formulation consisted of 3.25% phospholipid, 15% propylene glycol, and 10% ethanol. This optimized GLDL formulation demonstrated a 55.15% reduction in GCN release, a 4.67-fold enhancement in GCN permeation, and a 4.4-fold enhancement in GCN bioavailability over a 24-h period compared to free GCN. When compared to the DMBA-positive group, the nasal GLDL formulation resulted in a remarkable 97.65% reduction in tumor volume. The optimized GLDL exhibited antiproliferative properties, as demonstrated by histopathological analysis of the formulation. Furthermore, there was a notable 15.83-fold increase in the tumor accumulation of GCN in the nasal GLDL group compared to the oral GCN group. Importantly, the nasal GLDL formulation did not adversely affect erythropoiesis, immune function, or liver and kidney functions. The nasal GLDL spray is anticipated to be a promising and effective treatment option for BC.