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<p>Gemcitabine (GEM) is a potent chemotherapeutic agent, but its clinical utility is hindered by a short biological half-life and poor membrane permeability. To overcome these limitations and reduce systemic toxicity, we developed ultra-deformable transferosomes (ULT) integrated into a localized scaffold system to provide sustained drug release at the tumor site. in which, GEM was incorporated into ultra-deformable transferosomes (ULT) using a modified ethanol injection method, achieving high entrapment efficiency (~ 85%) and drug-loading capacity (~ 4%). These GEM-loaded transferosomes were further integrated into a CGTLS scaffold designed for localized post-mastectomy drug delivery. The formulation prolonged GEM stability, enhanced circulation time, and minimized systemic toxicity. In vitro drug release followed Korsmeyer–Peppas kinetics, confirming a sustained release profile. The scaffold exhibited high porosity (~ 70%), a swelling index of ~ 180%, osmolarity within the physiological range (275–300 mOsm/L), and a low contact angle (~ 19°), indicating a hydrophilic surface favourable for cell adhesion. High swelling capacity facilitated water uptake, drug diffusion, and improved interaction with tumor tissue. The scaffold demonstrated excellent biocompatibility, with 95.6% blood compatibility, along with sufficient mechanical strength and interconnected pores, yielding a diffusion coefficient of ~ 0.04&#xa0;cm²/s to support controlled GEM release. In vitro cytotoxicity studies using MCF-7 breast cancer cells showed significantly enhanced toxicity of the scaffold formulation compared to free GEM at 24 and 48&#xa0;h. Anticancer efficacy and apoptosis induction were confirmed through immunofluorescence, cellular internalization, qualitative apoptosis assays, ROS generation, DAPI nuclear staining, and migration and invasion studies, demonstrating caspase-7 activation, oxidative stress, nuclear alterations, and reduced metastatic potential. Overall, the CGTLS scaffold offers controlled drug delivery, favorable physicochemical properties, and potent anticancer activity, making it a promising localized post-adjuvant therapeutic system for mastectomy patients.</p> Graphical Abstract <p></p>

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Gemcitabine Loaded Ultra-deformable Transferosomes Based Scaffolds for the Breast Cancer Management

  • 期刊论文

  • 发表日期：

    2026年4月2日

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  • Manisha Busiraju,
  • Sandeep Chary Padakanti,
  • Bhavana Valamla,
  • Neelesh Kumar Mehra

摘要

Gemcitabine (GEM) is a potent chemotherapeutic agent, but its clinical utility is hindered by a short biological half-life and poor membrane permeability. To overcome these limitations and reduce systemic toxicity, we developed ultra-deformable transferosomes (ULT) integrated into a localized scaffold system to provide sustained drug release at the tumor site. in which, GEM was incorporated into ultra-deformable transferosomes (ULT) using a modified ethanol injection method, achieving high entrapment efficiency (~ 85%) and drug-loading capacity (~ 4%). These GEM-loaded transferosomes were further integrated into a CGTLS scaffold designed for localized post-mastectomy drug delivery. The formulation prolonged GEM stability, enhanced circulation time, and minimized systemic toxicity. In vitro drug release followed Korsmeyer–Peppas kinetics, confirming a sustained release profile. The scaffold exhibited high porosity (~ 70%), a swelling index of ~ 180%, osmolarity within the physiological range (275–300 mOsm/L), and a low contact angle (~ 19°), indicating a hydrophilic surface favourable for cell adhesion. High swelling capacity facilitated water uptake, drug diffusion, and improved interaction with tumor tissue. The scaffold demonstrated excellent biocompatibility, with 95.6% blood compatibility, along with sufficient mechanical strength and interconnected pores, yielding a diffusion coefficient of ~ 0.04 cm²/s to support controlled GEM release. In vitro cytotoxicity studies using MCF-7 breast cancer cells showed significantly enhanced toxicity of the scaffold formulation compared to free GEM at 24 and 48 h. Anticancer efficacy and apoptosis induction were confirmed through immunofluorescence, cellular internalization, qualitative apoptosis assays, ROS generation, DAPI nuclear staining, and migration and invasion studies, demonstrating caspase-7 activation, oxidative stress, nuclear alterations, and reduced metastatic potential. Overall, the CGTLS scaffold offers controlled drug delivery, favorable physicochemical properties, and potent anticancer activity, making it a promising localized post-adjuvant therapeutic system for mastectomy patients.

Graphical Abstract