A critical comparative insight on nanocarrier-based intranasal delivery of statins for neuroprotective applications

The incidence of central nervous system (CNS) disorders is rising globally, particularly as the prevalence of neurodegenerative diseases increases. The primary challenge in such cases is limited transport of therapeutics through the blood-brain barrier (BBB). Statins, widely used for hypercholesterolemia, exhibit pleiotropic neuroprotective effects; however, their therapeutic potential in CNS disorders is restricted by poor brain bioavailability with conventional routes. Intranasal (IN) delivery has long been recognized as a plausible pathway for brain targeting. This narrative review critically examines preclinical literature on IN nanocarrier-based delivery systems developed specifically for statins, with emphasis on nose-to-brain transport, formulation strategies, pharmacokinetics (PK), and neuroprotective outcomes. This work uniquely integrates a formulation-centric comparison of IN nanocarriers for statins. It highlights the potential of IN delivery, discussing the influence of carrier type, physicochemical properties, and delivery strategy on brain targeting efficiency and therapeutic relevance across different neurological indications. IN nanocarrier systems display potential to enhance statin brain delivery by bypassing the BBB and first-pass metabolism. Nevertheless, current evidence is predominantly preclinical, with significant variability in study design, pharmacokinetic reporting, and safety evaluation. Translation to clinics will require standardized nose-to-brain metrics, long-term safety studies, scalable manufacturing processes, and early regulatory alignment.