title: Systematic in vitro and in vivo study on porous silicon to improve the oral bioavailability of celecoxib.
abstract: Mesoporous materials are promising candidates for improving dissolution rate of poorly water-soluble drugs in vitro and their bioavailability in vivo. In the present study, sixteen batches of celecoxib-loaded PSi particles with pore sizes ranging from 17 to 58 nm and celecoxib content from 5 to 36 w-% were prepared and a detailed physicochemical characterization of the drug was performed by several methods. Interaction between co-culture of Caco-2/HT29-MTX cells and unloaded PSi particles was tested in toxicity assays, and increased toxicity for particles with large pore size was observed. Dissolution rate of celecoxib was improved in vitro by lowering the drug loading degree which hindered the recrystallization of celecoxib on the external surface of the particles. The fastest permeation of loaded celecoxib through the co-culture monolayer as well as the highest bioavailability in rats was observed with the particles with small pore size and low loading degree. New insights were obtained on how various parameters of the mesoporous delivery system affect the state of the drug inside the pores and its release in vitro and in vivo.
authors.affiliation: Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Joakim
authors.initials: J
authors.lastname: Riikonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: Institute of Biomedicine and Biocenter of Oulu, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Miia
authors.initials: M
authors.lastname: Kovalainen
authors.affiliation: Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Simo
authors.initials: S
authors.lastname: Näkki
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Leppänen
authors.affiliation: Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Jimi
authors.initials: J
authors.lastname: Rantanen
authors.affiliation: Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Wujun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; INEB - Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal.
authors.forename: Francisca
authors.initials: F
authors.lastname: Araújo
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, FI-70211 Kuopio, Finland. Electronic address: vesa-pekka.lehto@uef.fi.
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D000068579:Celecoxib / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018920:Coculture Techniques; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008297:Male; D010316:Particle Size; D016062:Porosity; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000737:chemistry*; D012995:Solubility
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D000068579:Celecoxib; D012825:Silicon
keywords: Biocompatibility; Cytotoxicity; Drug delivery; Drug release; Porosity; Silicon