Systematic in vitro and in vivo study on porous silicon to improve the oral bioavailability of celecoxib

• Published in: Biomaterials Vol. 52; pp. 44 - 55
• Main Authors: Riikonen, Joakim, Correia, Alexandra, Kovalainen, Miia, Näkki, Simo, Lehtonen, Marko, Leppänen, Jukka, Rantanen, Jimi, Xu, Wujun, Araújo, Francisca, Hirvonen, Jouni, Järvinen, Kristiina, Santos, Hélder A, Lehto, Vesa-Pekka
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2015
• Subjects: Administration, Oral; Advanced Basic Science; Animals; Bioavailability; Biocompatibility; Biological Availability; Biomedical materials; Caco-2 Cells; Celecoxib - administration & dosage; Celecoxib - pharmacokinetics; Coculture Techniques; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - pharmacokinetics; Cytotoxicity; Dentistry; Drug Carriers - chemistry; Drug delivery; Drug release; Drugs; Humans; In vitro testing; In vivo tests; Male; Particle Size; Porosity; Rats, Sprague-Dawley; Silicon; Silicon - chemistry; Solubility; Surgical implants; Drug release; Biocompatibility; Cytotoxicity; Drug delivery; Silicon; Porosity
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.02.014

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.