Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration

Abstract BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57...

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Main Authors:	Chrysanthi Tsika, Manolis N. Tzatzarakis, Sophia G. Antimisiaris, Pavlina Tsoka, Paschalis Efstathopoulos, Ioannis Charalampopoulos, Achille Gravanis, Miltiadis K. Tsilimbaris
Format:	Article
Language:	English
Published:	Wiley 2021-04-01
Series:	Pharmacology Research & Perspectives
Subjects:	blood–retinal barrier BNN27 LC‐MS neuroprotection pharmacokinetics steroids
Online Access:	https://doi.org/10.1002/prp2.724

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spelling	doaj-fcd72151d3b14d8da35170e8a31560b32021-10-01T09:16:18ZengWileyPharmacology Research & Perspectives2052-17072021-04-0192n/an/a10.1002/prp2.724Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administrationChrysanthi Tsika0Manolis N. Tzatzarakis1Sophia G. Antimisiaris2Pavlina Tsoka3Paschalis Efstathopoulos4Ioannis Charalampopoulos5Achille Gravanis6Miltiadis K. Tsilimbaris7Laboratory of Vision and Optics, Ophthalmology, Medical School University of Crete, Voutes Heraklion GreeceLaboratory of Toxicology, Medical School University of Crete Heraklion GreeceLaboratory of Pharmaceutical Technology, Department of Pharmacy University of Patras Rio GreeceLaboratory of Vision and Optics, Ophthalmology, Medical School University of Crete, Voutes Heraklion GreeceLaboratory of Pharmacology, Medical School University of Crete Heraklion GreeceLaboratory of Pharmacology, Medical School University of Crete Heraklion GreeceLaboratory of Pharmacology, Medical School University of Crete Heraklion GreeceLaboratory of Vision and Optics, Ophthalmology, Medical School University of Crete, Voutes Heraklion GreeceAbstract BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant kel = 0.465 h−1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (Cmax) in the retina was detected at 2 h (tCmax) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.https://doi.org/10.1002/prp2.724blood–retinal barrierBNN27LC‐MSneuroprotectionpharmacokineticssteroids
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Chrysanthi Tsika Manolis N. Tzatzarakis Sophia G. Antimisiaris Pavlina Tsoka Paschalis Efstathopoulos Ioannis Charalampopoulos Achille Gravanis Miltiadis K. Tsilimbaris
spellingShingle	Chrysanthi Tsika Manolis N. Tzatzarakis Sophia G. Antimisiaris Pavlina Tsoka Paschalis Efstathopoulos Ioannis Charalampopoulos Achille Gravanis Miltiadis K. Tsilimbaris Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration Pharmacology Research & Perspectives blood–retinal barrier BNN27 LC‐MS neuroprotection pharmacokinetics steroids
author_facet	Chrysanthi Tsika Manolis N. Tzatzarakis Sophia G. Antimisiaris Pavlina Tsoka Paschalis Efstathopoulos Ioannis Charalampopoulos Achille Gravanis Miltiadis K. Tsilimbaris
author_sort	Chrysanthi Tsika
title	Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration
title_short	Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration
title_full	Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration
title_fullStr	Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration
title_full_unstemmed	Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration
title_sort	quantification of bnn27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration
publisher	Wiley
series	Pharmacology Research & Perspectives
issn	2052-1707
publishDate	2021-04-01
description	Abstract BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant kel = 0.465 h−1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (Cmax) in the retina was detected at 2 h (tCmax) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.
topic	blood–retinal barrier BNN27 LC‐MS neuroprotection pharmacokinetics steroids
url	https://doi.org/10.1002/prp2.724
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Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration

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