CNS Delivery and Anti-Inflammatory Effects of Intranasally-Administered Cyclosporine-A in Cationic Nanoemulsion Formulations

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 cationic oil-in-water nanoemulsion system upon intranasal administration. We have utilized omega-3 fatty acid rich flaxseed oil-based nanoemulsion for intranasal delivery to brain and further used magnetic resonance imaging (MRI) to evaluate and confirm transport of the nanoemulsion in CNS. Furthermore, we have evaluated the anti-inflammatory potential of CsA peptide using the lipopolysaccharide (LPS) model of neuroinflammation in rats. CsA nanoemulsion showed had a good safety profile when tested in vitro in RPMI2650 cells. Upon intranasal administration in rats, nanoemulsion delivery system showed higher uptake in major regions of brain when dosed intranasally based on changes in the MR T1 relaxivity values. Additionally, CsA nanoemulsion showed improved therapeutic efficacy by inhibiting proinflammatory cytokines in the LPS stimulated rat model of neuroinflammation as compared to 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 peptide may provide a clinically-translatable strategy for treating neurological diseases.