title: Nanocarriers and the delivered drug: effect interference due to intravenous administration.
abstract: Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself.
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland. Electronic address: maria.vlasova@uef.fi.
authors: Maria A
authors: MA
authors: Vlasova
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
authors: Jussi
authors: J
authors: Rytkönen
authors: Faculty of Science and Forestry, Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland. Electronic address: joakim.riikonen@uef.fi.
authors: Joakim
authors: J
authors: Riikonen
authors: Department of Human and Animal Physiology, M.V. Lomonosov Moscow State University, Moscow 119234, Russia. Electronic address: ost.msu@gmail.com.
authors: Olga S
authors: OS
authors: Tarasova
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
authors: Juha
authors: J
authors: Mönkäre
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
authors: Miia
authors: M
authors: Kovalainen
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
authors: Ale
authors: A
authors: Närvänen
authors: Department of Physics and Astronomy, University of Turku, 20014 Turku, Finland. Electronic address: jarno.salonen@utu.fi.
authors: Jarno
authors: J
authors: Salonen
authors: Institute of Biomedicine & Biocenter of Oulu, University of Oulu, 90014 Oulu, Finland. Electronic address: karl-heinz.herzig@oulu.fi.
authors: Karl-Heinz
authors: KH
authors: Herzig
authors: Faculty of Science and Forestry, Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland. Electronic address: vesa-pekka.lehto@uef.fi.
authors: Vesa-Pekka
authors: VP
authors: Lehto
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland. Electronic address: kristiina.jarvinen@uef.fi.
authors: Kristiina
authors: K
authors: Järvinen
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D016477:Artifacts; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D054439:Ghrelin / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012825:Silicon / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D054439:Ghrelin; D010455:Peptides; D001262:Atenolol; D012825:Silicon
keywords: Arterial pressure; Atenolol (PubChem CID: 2249); Chloramine T (PubChem CID: 3641960); Drug delivery; Ethanol (PubChem CID: 702); HEPES (PubChem CID: 23831); Hydrofluoric acid (PubChem CID: 14917); Intravenous; Lipopolysacharide (PubChem CID: 11970143); Mesoporous silicon (calcium silicate) (PubChem CID: 26370); Nanoparticles; Sodium chloride (PubChem CID: 5234); Tween 20 (PubChem CID: 443314); [D-Lys-3]-GHRP-6 (PubChem CID: 5311279)