A review on intranasal nanoparticle delivery systems for blood–brain barrier penetration in medulloblastoma therapeutics: current insights and future perspectives

Accounting for approximately 20% of all childhood central nervous system (CNS) malignancies, medulloblastoma is the most common malignant pediatric brain tumor. Current standard-of-care treatment, comprising craniospinal irradiation, adjuvant chemotherapy, and surgical resection remain associated with significant neurocognitive and systemic toxicity, particularly in young patients. A significant obstacle in pharmacological management is the blood–brain barrier (BBB), which limits the channel of most therapeutic agents into the CNS, severely restraining drug bioavailability at the tumor location. Intranasal (IN) drug delivery has come into light as a potential non-invasive approach to circumvent the BBB and attain direct transportation through the trigeminal and olfactory nerve pathways. This method reduces peripheral side effects, facilitates rapid drug transport to the CNS and avoids systemic circulation. Nonetheless, the nasal epithelium offers its own physicochemical barriers, including enzymatic degradation and mucociliary clearance (MCC), which reduce the effectiveness of traditional formulations. Nanoparticle (NP)-based drug delivery systems provide a convincing answer to these challenges. Lipid-based carriers, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nano emulsions (NEs), and liposomes, along with polymer-based systems such as PLGA, alginate NPs and chitosan, have showed controlled drug release, improved mucoadhesion, targeted delivery and improved CNS bioavailability. Surface modifications with receptor-targeting ligands, permeation enhancers and PEG, further enhance their therapeutic potential. This review critically evaluates the present landscape of IN-NP-based approaches for medulloblastoma treatment, discussing transport mechanisms, formulation design, preclinical evidence, and translational obstacles to clinical applications. Graphical abstract for intranasal nanoparticle-mediated delivery for targeted medulloblastoma therapy. This graphic pictorial illustrates the intranasal delivery of nanoparticles through olfactory and trigeminal pathways, enabling blood–brain barrier penetration, targeted medulloblastoma treatment, and improved therapeutic outcomes with reduced systemic toxicity.