Lipid polymeric nanoparticles modified with tight junction-modulating peptides promote afatinib delivery across a blood–brain barrier model

Abstract Background Brain metastases from non-small cell lung cancer (NSCLC) remain one of the most challenging malignancies. Afatinib (Afa) is an orally administered irreversible ErbB family blocker approved for epidermal growth factor receptor (EGFR)-mutated NSCLC. However, incidence brain in patients with NSCLC and EGFR mutation high. One major obstacles treatment to transport drugs across blood–brain barrier (BBB). A lipid polymeric nanoparticle (LPN) modified a tight junction-modulating peptide potential formulation deliver therapeutics BBB. FD7 CCD are short peptides that perturb junctions (TJs) In this study, use LPN or as delivery platform was explored enhance Afa BBB model mouse brain-derived endothelial bEnd.3 cells. Results Our findings revealed Afa/LPN-FD7 Afa/LPN-CCD exhibited homogeneous shape, uniform nano-scaled particle size, sustained-release profile. FD7, CCD, Afa/LPN-FD7, did not cause significant cytotoxic effect on cells enhanced cytotoxicity human adenocarcinoma PC9 CCD-modulated TJ proteins, such claudin 5 ZO-1, reduced transendothelial electrical resistance, increased permeability paracellular markers were also partially transported through clathrin- caveolae-mediated transcytosis, revealing effective activation transcellular pathways facilitate Conclusion TJ-modulating peptide-modified could be prospective chemotherapeutics BM