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<p>Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, has poor solubility and non-specific distribution, which limit its clinical effectiveness in NSCLC. To improve pulmonary delivery, OSI-loaded bovine lactoferrin nanoparticles (OSI@LFNPs) were developed and compared with OSI-loaded albumin nanoparticles (OSI@AlbNPs) using a desolvation method followed by glutaraldehyde crosslinking. These particles were characterized by DLS, zeta potential analysis, and FE-SEM. OSI@LFNPs showed a hydrodynamic size of 224.9 ± 18.1&#xa0;nm, an acceptable polydispersity index (PDI) value, and a zeta potential of − 50.47 ± 12.23 mV, while OSI@AlbNPs measured 407.0 ± 125.1&#xa0;nm with a nearly neutral surface charge (0 ± 0 mV). FE-SEM images confirmed the presence of well-formed protein-based nanoparticles, with lactoferrin displaying smoother surfaces compared to the rougher, clefted structure of albumin. Encapsulation efficiency and loading capacity were 49.03 ± 2.60% and 54.54 ± 2.89% for LFNPs, versus 38.99 ± 1.33% and 43.38 ± 1.48% for AlbNPs, respectively, with low polydispersity indicating uniform dispersions. Release studies revealed temperature- and pH-responsive behavior; kinetic modeling showed a first-order release for LFNPs (R²=0.9929) and Higuchi diffusion for AlbNPs (R²=0.9803). In vivo biodistribution in rats showed significantly higher lung accumulation with LFNPs (33.64 ± 1.26% of the injected dose) compared to AlbNPs (15.27 ± 1.45%) and free OSI (18.47 ± 2.83%) (<i>p</i> &lt; 0.001), along with reduced renal uptake relative to AlbNPs. Overall, LFNPs offer higher drug loading, favorable colloidal properties, controlled release, and superior lung targeting, supporting their potential as a biocompatible carrier to enhance OSI bioavailability and therapeutic efficacy in NSCLC.</p>

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Bovine Colostrum-Derived Lactoferrin Nanoparticles as a Novel Platform for Improved Pulmonary Delivery of Osimertinib

  • 期刊论文

  • 发表日期：

    2025年10月24日

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  • Zainab Sabri Abbas,
  • Zaizafoon N. Nasif,
  • Amer T. Tawfeeq

摘要

Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, has poor solubility and non-specific distribution, which limit its clinical effectiveness in NSCLC. To improve pulmonary delivery, OSI-loaded bovine lactoferrin nanoparticles (OSI@LFNPs) were developed and compared with OSI-loaded albumin nanoparticles (OSI@AlbNPs) using a desolvation method followed by glutaraldehyde crosslinking. These particles were characterized by DLS, zeta potential analysis, and FE-SEM. OSI@LFNPs showed a hydrodynamic size of 224.9 ± 18.1 nm, an acceptable polydispersity index (PDI) value, and a zeta potential of − 50.47 ± 12.23 mV, while OSI@AlbNPs measured 407.0 ± 125.1 nm with a nearly neutral surface charge (0 ± 0 mV). FE-SEM images confirmed the presence of well-formed protein-based nanoparticles, with lactoferrin displaying smoother surfaces compared to the rougher, clefted structure of albumin. Encapsulation efficiency and loading capacity were 49.03 ± 2.60% and 54.54 ± 2.89% for LFNPs, versus 38.99 ± 1.33% and 43.38 ± 1.48% for AlbNPs, respectively, with low polydispersity indicating uniform dispersions. Release studies revealed temperature- and pH-responsive behavior; kinetic modeling showed a first-order release for LFNPs (R²=0.9929) and Higuchi diffusion for AlbNPs (R²=0.9803). In vivo biodistribution in rats showed significantly higher lung accumulation with LFNPs (33.64 ± 1.26% of the injected dose) compared to AlbNPs (15.27 ± 1.45%) and free OSI (18.47 ± 2.83%) (p < 0.001), along with reduced renal uptake relative to AlbNPs. Overall, LFNPs offer higher drug loading, favorable colloidal properties, controlled release, and superior lung targeting, supporting their potential as a biocompatible carrier to enhance OSI bioavailability and therapeutic efficacy in NSCLC.