Nose to Brain: Exploring the Progress of Intranasal Delivery of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers

The intranasal (IN) route of drug delivery can effectively penetrate the blood-brain barrier and deliver drugs directly to the brain for the treatment of central nervous system (CNS) disorders via intra-neuronal or extra-neuronal pathways. This approach has several advantages, including avoidance of first-pass metabolism, high bioavailability, ease of administration, and improved patient compliance. In recent years, an increasing number of studies have been conducted using drugs encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and delivering them to the brain via the IN pathway. SLNs are the first-generation solid lipid nanocarriers, known for their excellent biocompatibility, high drug-loading capacity, and remarkable stability. NLCs, regarded as the second-generation SLNs, not only retain the advantages of SLNs but also exhibit enhanced stability, effectively preventing drug leakage during storage. In this review, we examined in vivo studies conducted between 2019 and 2024 that used SLNs and NLCs to address CNS disorders via the IN route. By using statistical methods to evaluate pharmacokinetic parameters, we found that IN delivery of SLNs and NLCs markedly enhanced drug accumulation and targeting within the brain. Additionally, pharmacodynamic evaluations indicated that this delivery method substantially improved the therapeutic effectiveness of the drugs in alleviating symptoms in rat models of CNS diseases. In addition, methods for enhancing the efficacy of nose-to-brain delivery of SLNs and NLCs are discussed, as well as advances in clinical trials regarding SLNs and NLCs.