Formulation Innovations for EGFR-Targeted Breast Cancer Therapy: Enhancing Delivery and Efficacy

Abstract

Breast cancer, particularly aggressive subtypes like triple-negative breast cancer (TNBC), is propelled by epidermal growth factor receptor (EGFR) overexpression, contributing to tumor proliferation and therapeutic resistance. Conventional EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, face significant hurdles including poor aqueous solubility, rapid systemic clearance, and off-target toxicity, which compromise their efficacy and patient tolerability. This review synthesizes recent innovations in advanced delivery systems to overcome these limitations, emphasizing enhanced selectivity, bioavailability, and reduced adverse effects. Key advancements include nanoemulsions, liposomes, and phytosomal carriers tailored for EGFR inhibitors. Nanoemulsions improve drug encapsulation and tumor permeability via the enhanced permeability and retention (EPR) effect, achieving up to 2-3-fold bioavailability gains in breast cancer models. Liposomes enable ligand-mediated targeting (e.g., EGFR-specific antibodies) and stimuli-responsive release, minimising cardiotoxicity while boosting apoptosis in TNBC cells. Phytosomal complexes enhance the solubility of lipophilic TKIs and phytochemicals, promoting sustained release and hepatic protection. Synergistic co-delivery strategies incorporating natural antioxidants—curcumin, Moringa oleifera extracts, and wheatgrass bioactives—further amplify outcomes by attenuating reactive oxygen species (ROS), inflammation, and drug resistance pathways. Preclinical data demonstrate superior tumour regression with curcumin-EGFR TKI combinations in nanoparticle formulations. Artificial intelligence (AI)-driven approaches, leveraging machine learning for predictive modelling of particle size, ligand density, and pharmacokinetics, optimise tumour homing and blood-brain barrier penetration for metastatic disease.