Therapeutic effect of cyclosporine A-loading TPGS micelles on a mouse model of LPS-induced neuroinflammation.

Abstract

Neuroinflammation is an undoubted hallmark of neurodegenerative processes characterized by memory impairment, loss of coordination and muscle strength in diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as depressive disorders. Cyclosporine A (CSA) has already been identified as a promising neuroprotective peptide, due to its well-known anti-inflammatory properties. Herein, CSA was encapsulated into α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles and intranasally administered to a lipopolysaccharide (LPS) induced mouse model of neuroinflammation. After the treatment, mice were subjected to behavioral tests to assess cognitive and motor skills, while the biodistribution of CSA in plasma and olfactory bulb was studied by a new HPLC method validated for precision and accuracy. The results highlighted that in comparison to the classic oral CSA suspension, the intranasal (IN) administration showed significatively better safety and efficiency profiles. Notably, IN administration of CSA micelles showed relevant antidepressive effects and a certain ability to revert LPS-induced motor impairment. This work pointed out that the innovative and noninvasive IN administration of TPGS micelles could represent a safe and effective alternative to the classic oral route to deliver CSA at the Central Nervous System level, where its beneficial activity against neuroinflammation can be exploited.