PT  - JOURNAL ARTICLE
AU  - Sunita Yadav
AU  - Grishma Pawar
AU  - Praveen Kulkarni
AU  - Craig Ferris
AU  - Mansoor Amiji
TI  - CNS Delivery and Anti-Inflammatory Effects of Intranasally Administered Cyclosporine-A in Cationic Nanoformulations
AID  - 10.1124/jpet.118.254672
DP  - 2019 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 843--854
VI  - 370
IP  - 3
4099  - http://jpet.aspetjournals.org/content/370/3/843.short
4100  - http://jpet.aspetjournals.org/content/370/3/843.full
SO  - J Pharmacol Exp Ther2019 Sep 01; 370
AB  - The main objective of this study was to develop and evaluate the CNS delivery efficiency, distribution, therapeutic efficacy, and safety of cyclosporine A (CSA) using a cationic oil-in-water nanoemulsion system upon intranasal administration. An omega-3 fatty acid–rich, flaxseed oil–based nanoemulsion was used for intranasal delivery to the brain, and further magnetic resonance imaging (MRI) was used to evaluate and confirm the transport of the positively charged CSA nanoemulsion (CSA-NE) in CNS. Furthermore, the anti-inflammatory potential of CSA peptide was evaluated using the lipopolysaccharide (LPS) model of neuroinflammation in rats. CSA-NE showed a good safety profile when tested in vitro in RPMI 2650 cells. Upon intranasal administration in rats, the nanoemulsion delivery system showed higher uptake in major regions of the brain based on changes in MRI T1 (longitudinal relaxation time) values. Additionally, CSA nanoemulsion showed improved therapeutic efficacy by inhibiting proinflammatory cytokines in the LPS-stimulated rat model of neuroinflammation compared with solution formulation. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects in rats. Based on these results, intranasal delivery of CSA and other “neuroprotective peptides” may provide a clinically translatable strategy for treating neurologic diseases.