title: In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart.
abstract: Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Marja A
authors.initials: MA
authors.lastname: Tölli
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Mónica P A
authors.initials: MP
authors.lastname: Ferreira
authors.affiliation: Division of Pharmacology and Pharmacotherapy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Sini M
authors.initials: SM
authors.lastname: Kinnunen
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szabó
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland; Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Raisa E
authors.initials: RE
authors.lastname: Serpi
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Pauli J
authors.initials: PJ
authors.lastname: Ohukainen
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Mika J
authors.initials: MJ
authors.lastname: Välimäki
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Alexandra M R
authors.initials: AM
authors.lastname: Correia
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FI-90014 Oulu, Finland; Division of Pharmacology and Pharmacotherapy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: heikki.ruskoaho@helsinki.fi.
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Ruskoaho
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry*; D002478:Cells, Cultured; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D016503:Drug Delivery Systems; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D012825:Silicon
keywords: Biocompatibility; Cardiac delivery; Microparticles; Myocardial infarction; Nanoparticles; Porous silicon