Receptor-mediated nose-to-brain delivery of drug combination-loaded polymeric nanocarriers for the treatment of glioblastoma- current progress and future perspectives part I: receptor-mediated nose-to-brain delivery approaches for glioblastoma.

[INTRODUCTION] Glioblastoma multiforme (GBM) is a highly aggressive tumor with poor survival rates. Current treatment strategies are hindered by blood - brain barrier (BBB), which limits the delivery of medication, and by systemic toxicity and insufficient drug levels at the tumor site. A promising new approach, nose-to-brain delivery, offers noninvasive way to bypass the BBB through the olfactory and trigeminal pathways, allowing for direct brain targeting. One promising method, receptor-mediated transport, utilizes receptors found on nasal epithelial cells and glioblastoma cells to enhance drug uptake at the tumor site. However, this approach faces challenges, including difficulties with mucociliary clearance, dosing issues, and variations in medication response among patients.

[AREA COVERED] This review offers an overview of receptor-mediated nose-to-brain delivery strategies for GBM. It focuses on nasal pathways, transport mechanisms, and key receptors, including transferrin, insulin, folate, and integrins. The review highlights that targeting these receptors can enhance delivery efficiency, increase brain penetration, and facilitate the co-delivery of drugs to address tumor heterogeneity and resistance.

[EXPERT OPINION] Receptor-mediated intranasal delivery offers a promising strategy for GBM therapy. Advancing this approach will require precise receptor targeting and robust clinical validation to ensure effective translation from bench to bedside.