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Nanocarriers and the delivered drug: effect interference due to intravenous administration.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (2014-06-26)
Maria A Vlasova, Jussi Rytkönen, Joakim Riikonen, Olga S Tarasova, Juha Mönkäre, Miia Kovalainen, Ale Närvänen, Jarno Salonen, Karl-Heinz Herzig, Vesa-Pekka Lehto, Kristiina Järvinen
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.

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