title: Comparative pharmacokinetics and tissue distribution analysis of systemically administered 17-β-estradiol and its metabolites in vivo delivered using a cationic nanoemulsion or a peptide-modified nanoemulsion system for targeting atherosclerosis.
abstract: The primary objective of this study was to compare the biodistribution and pharmacokinetic profile of 17-β-estradiol (17-βE) on systemic delivery using either the cationic or the CREKA-peptide-modified (Cysteine-Arginine-Glutamic-acid-Lysine-Alanine) omega-3-fatty acid oil containing nanoemulsion system in vivo in the wild type C57BL/6 mice. Higher blood concentrations of 17-βE, higher accumulation in the tissues of interest - heart and aorta, and higher accumulation within the other tissues - liver and kidney was observed on delivering 17-βE using the CREKA-peptide-modified nanoemulsion system (AUClast in plasma - 263.89±21.81min*%/injected dose/ml) as compared to the cationic nanoemulsion (AUClast in plasma - 20.2±1.86min*%/injected dose/ml) and solution form (AUClast in plasma - 44.9±1.24min*%/injected dose/ml) respectively. Both, the cationic nanoemulsion and the CREKA-peptide-modified nanoemulsion showed a higher relative targeting efficiency of 4.57 and 4.86 respectively for 17-βE than the relative targeting efficiency of 1.78 observed with the solution form. In conclusion, since the maximum exposure (highest AUClast for plasma and tissues) for 17-βE was observed with the CREKA-peptide-modified nanoemulsion system, the study shows that CREKA-peptide-modified nanoemulsion system was the most suitable vehicle for systemic delivery of 17-βE in the wild type C57BL/6 mice.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston 02115-5000, USA.
authors.forename: Dipti
authors.initials: D
authors.lastname: Deshpande
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston 02115-5000, USA.
authors.forename: Sravani
authors.initials: S
authors.lastname: Kethireddy
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston 02115-5000, USA; Department of Pharmacokinetics, EA4215 Faculté de Pharmacie, Université Montpellier 1, 15 av. Ch. Flahault, 34093 Montpellier Cedex 5, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Gattacceca
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston 02115-5000, USA. Electronic address: m.amiji@neu.edu.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D002412:Cations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D015525:Fatty Acids, Omega-3 / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D002412:Cations; D004337:Drug Carriers; D004655:Emulsions; D015525:Fatty Acids, Omega-3; D009842:Oligopeptides; C542438:cysteinyl-arginyl-glutamyl-lysyl-alanyl; D004958:Estradiol
keywords: 17-βE; Atherosclerosis; CREKA; DOTAP; Nanoemulsion; Targeting efficiency