Background: Multiple sclerosis (MS) is one of the most severe autoimmune disorder of the central nervous system (CNS). Objective: The present research work was aimed to formulate and investigate teriflunomide (TFM) loaded intranasal (i.n.) nanostructured lipid carriers (NLC) for the treatment of multiple sclerosis (MS). Methods: The TFM-loaded NLC (TFM-NLC) nanoparticles were prepared by melt emulsification ultrasonication method using biodegradable and biocompatible polymers. The Box-Behnken statistical design was applied to optimize the formulation. The optimized NLC formulation was subjected to evaluate for particle size, entrapment efficiency (%), in vitro and ex vivo permeation. The safety and efficacy of optimized formulations were demonstrated using pharmacodynamic, sub-acute toxicity and hepatotoxicity data. Results: Experimental data demonstrated that optimized NLC formulation (F17) showed significant size (99.82 ± 1.36 nm), zeta potential (-22.29 ± 1.8 mV) and % entrapment efficiency (83.39 ± 1.24%). Alternatively, ex vivo permeation of TFM mucoadhesive NLC (TFM-MNLC) and TFM-NLC was observed 830 ± 7.6 and 651 ± 9.8 µg/cm² respectively. Whereas, TFM-MNLC shows around 2.0 folds more J_ss than the TFM-NLC. Finally, TFM-MNLC (i.n.) formulation produced the rapid remyelination in cuprizone treated animals and decreases the number of entries in open compartment of EPM when compared with negative control and TFM-NLC (oral) animals. Simultaneously, the nanoformulation didn’t reflect any gross changes in hepatic biomarkers and sub-acute toxicity when compared with control. Conclusions: Hence it can be inferred that the nose-to-brain delivery of TFM-MNLC can be considered as effective and safe delivery for brain disorders.

Alzheimer's disease (AD) is still an excessively complicated neurological disorder that impacts millions of individuals globally. The ideal defensive feature of the central nervous system (CNS) is the intimate junction of endothelial cells, which functions as a biological barrier to safely control molecular transport throughout the brain. The blood-brain barrier (BBB) comprises tightly locked astrocyte cell junctions on CNS blood capillaries. This biological barrier shields the brain from hazardous toxins by preventing the entry of polar medications, cells, and ions. However, it is very challenging to provide any treatment to the brain for neurodegenerative illnesses like Alzheimer's. Different causative mechanisms, such as amyloid-β (Aβ) plaques, tubulin-associated unit (Tau) tangles, and neuroinflammation, cause neuronal dysfunction, leading to dementia and memory loss in the subject. Several treatments are approved for AD therapy, whereas most only help treat related symptoms. Disappointingly, current remedies have not been able to control the progression of AD due to associated side effects. Specific pathogenic mechanisms are involved in the initiation and development of this disease. Therefore, the expected survival of a patient with AD is limited and is approximately ten years. Hence, the pathogenic mechanism behind AD progression must be understood to better comprehend and improve the overall survival rate. This review highlighted the recent insights into AD pathogenesis, molecular mechanisms, advancements in theragnostic techniques, the existing updates of clinical trials, and emerging innovations for AD medicinal development. That has helped researchers develop other strategies to address the shortcomings of traditional medications.