CNS Delivery and Anti-Inflammatory Effects of Intranasally Administered Cyclosporine-A in Cationic Nanoformulations
| Autor: | Craig F. Ferris, Mansoor M. Amiji, Praveen Kulkarni, Sunita Yadav, Grishma Pawar |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Central Nervous System
Lipopolysaccharides Male 0301 basic medicine Linseed Oil Lipopolysaccharide medicine.drug_class Drug Compounding Pharmacology Neuroprotection Anti-inflammatory Cell Line Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Fatty Acids Omega-3 medicine Special Issue on Drug Delivery Technologies Animals Distribution (pharmacology) Administration Intranasal Neuroinflammation Inflammation business.industry Anti-Inflammatory Agents Non-Steroidal Magnetic Resonance Imaging In vitro Nanostructures Rats 030104 developmental biology chemistry Cyclosporine Cytokines Molecular Medicine Emulsions Nasal administration business 030217 neurology & neurosurgery |
| Zdroj: | J Pharmacol Exp Ther |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | 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 T(1) (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. |
| Databáze: | OpenAIRE |
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