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<p>Breast cancer (BC) continues to be a significant global health issue, with triple-negative breast cancer being one of the most aggressive forms. Palbociclib (PAL) has shown promising results in BC therapy but suffers from low solubility, poor oral bioavailability, and variable systemic absorption. A polymeric nanocapsule based on PAL-loaded dextran (PAL-DEX-PNC) was developed to enhance its solubility, stability, gastrointestinal tract (GIT) retention and anticancer efficacy. The optimised PAL-DEX-PNC exhibited a particle size, PDI, zeta potential and percentage entrapment efficiency of 217.8 ± 2.15&#xa0;nm, 0.24 ± 0.03, 1.72 ± 1.07&#xa0;mV, and 99.71 ± 3.1%, respectively. PAL-DEX-PNC had sufficient storage stability of 60&#xa0;days at 2–8°C, in simulated GIT conditions and DMEM cell culture media. The PAL release from PAL-DEX-PNC at pH 5.5 and 7.4 was 70.05 ± 3.02% and 62.46 ± 3.43%, respectively, sustained for a period of 48&#xa0;h. The <i>ex vivo</i> permeability studies confirmed an 8.85-fold increase in drug permeability for PAL-DEX-PNC compared to free PAL. The <i>in vitro</i> cytotoxicity assessment on MDA-MB-231 cells revealed that PAL-DEX-PNC has significantly greater cytotoxic potential than free PAL, with a 3.49-fold decreased IC<sub>50</sub> value and 2.22-fold enhanced apoptotic index. Furthermore, higher ROS production, depolarisation of MMP and cellular uptake, along with reduced colony formation and wound healing, were evidenced. In addition, a 3.19-fold reduction in 3D mammosphere diameter was seen with PAL-DEX-PNC. The <i>in vivo</i> GIT uptake studies depicted that Nile red-loaded polymeric nanocapsules exhibited 3.68-fold higher fluorescence intensity in the GIT than free Nile red, indicating higher uptake attributed to the mucoadhesive nature of DEX.</p> Graphical Abstract <p></p>

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Mucoadhesive Carbohydrate-Based Polymeric Nanocapsule Loaded with Palbociclib for Enhanced GIT Retention and In Vitro Anticancer Efficacy in MDA-MB-231 Cells

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • Pooja Khade,
  • Ujala Gupta,
  • Rahul Kumar,
  • Neelesh Kumar Mehra,
  • Pankaj Kumar Singh

摘要

Breast cancer (BC) continues to be a significant global health issue, with triple-negative breast cancer being one of the most aggressive forms. Palbociclib (PAL) has shown promising results in BC therapy but suffers from low solubility, poor oral bioavailability, and variable systemic absorption. A polymeric nanocapsule based on PAL-loaded dextran (PAL-DEX-PNC) was developed to enhance its solubility, stability, gastrointestinal tract (GIT) retention and anticancer efficacy. The optimised PAL-DEX-PNC exhibited a particle size, PDI, zeta potential and percentage entrapment efficiency of 217.8 ± 2.15 nm, 0.24 ± 0.03, 1.72 ± 1.07 mV, and 99.71 ± 3.1%, respectively. PAL-DEX-PNC had sufficient storage stability of 60 days at 2–8°C, in simulated GIT conditions and DMEM cell culture media. The PAL release from PAL-DEX-PNC at pH 5.5 and 7.4 was 70.05 ± 3.02% and 62.46 ± 3.43%, respectively, sustained for a period of 48 h. The ex vivo permeability studies confirmed an 8.85-fold increase in drug permeability for PAL-DEX-PNC compared to free PAL. The in vitro cytotoxicity assessment on MDA-MB-231 cells revealed that PAL-DEX-PNC has significantly greater cytotoxic potential than free PAL, with a 3.49-fold decreased IC50 value and 2.22-fold enhanced apoptotic index. Furthermore, higher ROS production, depolarisation of MMP and cellular uptake, along with reduced colony formation and wound healing, were evidenced. In addition, a 3.19-fold reduction in 3D mammosphere diameter was seen with PAL-DEX-PNC. The in vivo GIT uptake studies depicted that Nile red-loaded polymeric nanocapsules exhibited 3.68-fold higher fluorescence intensity in the GIT than free Nile red, indicating higher uptake attributed to the mucoadhesive nature of DEX.

Graphical Abstract