Comparative Biodistribution and Pharmacokinetic Analysis of Cyclosporine-A in the Brain upon Intranasal or Intravenous Administration in an Oil-in-Water Nanoemulsion Formulation

Molecular Pharmaceutics
Sunita YadavMansoor M Amiji

Abstract

The main objective of this study was to evaluate comparative biodistribution and pharmacokinetics of cyclosporine-A (CsA) following intranasal (IN) administration versus intravenous (IV) administration in Sprague-Dawley rats using an oil-in-water nanoemulsion delivery system. CsA, a hydrophobic peptide that is also a substrate for P-glycoprotein, is a well-known immunosuppressive agent. In the brain, CsA has been shown to be a potent anti-inflammatory and neuroprotective agent. CsA nanoemulsions (CsA-NE) and solution formulations (CsA-S) were prepared using an ultrasonication method and were characterized for drug content, encapsulation efficiency, globule size, and zeta potential. We compared the uptake of CsA-NE and CsA-S in brain regions and peripheral organs following IN and IV administration using LC-MS/MS based bioanalytical method. CsA-NE IN resulted in the highest accumulation compared to that with any other treatment and route of administration; this was consistent for all three regions of brain that were evaluated (olfactory bulbs, mid brain, and hind brain). The brain/blood exposure ratios of 4.49, 0.01, 0.33, and 0.03 for CsA-NE (IN), CsA-NE (IV), CsA-S (IN), and CsA-S (IV), respectively, indicated that CsA-NE is ca...Continue Reading

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Citations

Sep 1, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kathleen A RossBalaji Narasimhan
May 8, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Doaa Ahmed El-SetouhyEman S Elzanfaly
Jun 27, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Reham S ElezabyGehanne A Awad
Jan 31, 2020·Nanomedicine·Robert A Yokel
Dec 29, 2018·The Journal of Pharmacology and Experimental Therapeutics·Sunita YadavMansoor Amiji
Apr 17, 2020·Drug Delivery and Translational Research·Atinderpal KaurShweta Dang
Feb 20, 2019·Pharmaceutics·Maria Cristina BonferoniPaolo Giunchedi
Oct 4, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Inbar SchlachetAlejandro Sosnik
Jan 12, 2020·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Hussein AkelIldikó Csóka
Jul 1, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wei GaoQiang Zhang
May 5, 2020·Molecular Pharmaceutics·Harkiranpreet Kaur DhaliwalMansoor M Amiji
Nov 4, 2021·Drug Delivery and Translational Research·Mireya L Borrajo, María José Alonso

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