title: Cytotoxicity and apoptotic gene expression in an in vitro model of the blood-brain barrier following exposure to poly(butylcyanoacrylate) nanoparticles.
abstract: Background Poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) loaded with doxorubicin (DOX) and coated with polysorbate 80 (PS80) have shown efficacy in the treatment of rat glioblastoma. However, cytotoxicity of this treatment remains unclear. Purpose The purpose of this study was to investigate cytotoxicity and apoptotic gene expression using a proven in vitro co-culture model of the blood-brain barrier. Methods The co-cultures were exposed to uncoated PBCA NPs, PBCA-PS80 NPs or PBCA-PS80-DOX NPs at varying concentrations and evaluated using a resazurin-based cytotoxicity assay and an 84-gene apoptosis RT-PCR array. Results The cytotoxicity assays showed PBCA-PS80-DOX NPs exhibited a decrease in metabolic function at lower concentrations than uncoated PBCA NPs and PBCA-PS80 NPs. The apoptosis arrays showed differential expression of 18 genes in PBCA-PS80-DOX treated cells compared to the untreated control. Discussion As expected, the cytotoxicity assays demonstrated enhanced dose-dependent toxicity in the DOX loaded NPs. The differentially expressed apoptotic genes participate in both the tumor necrosis factor receptor-1 and mitochondria-associated apoptotic pathways implicated in current DOX chemotherapeutic toxicity. Conclusion The following data suggest that the cytotoxic effect may be attributed to DOX and not the NPs themselves, further supporting the use of PBCA-PS80 NPs as an effective drug delivery vehicle for treating central nervous system conditions.
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;|b Department of Chemistry , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hall
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Ruth
authors.initials: R
authors.lastname: Hemmer
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Robert
authors.initials: R
authors.lastname: Spaulding
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Hanna N
authors.initials: HN
authors.lastname: Wetzel
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Joseph
authors.initials: J
authors.lastname: Curcio
authors.affiliation: c Institute of Medical Psychology, Otto-von-Guericke University , Magdeburg , Germany ;
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Sabel
authors.affiliation: c Institute of Medical Psychology, Otto-von-Guericke University , Magdeburg , Germany ;
authors.forename: Petra
authors.initials: P
authors.lastname: Henrich-Noack
authors.affiliation: d Molecular and Cellular Physiology Department , University of Cincinnati Medical Center , Cincinnati , OH , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pixley
authors.affiliation: d Molecular and Cellular Physiology Department , University of Cincinnati Medical Center , Cincinnati , OH , USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Hopkins
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boyce
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Schultheis
authors.affiliation: a Department of Biological Sciences , Northern Kentucky University , Highland Heights , KY , USA ;
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Haik
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001253:Astrocytes / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D004659:Enbucrilate / Q000737:chemistry / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin; D004659:Enbucrilate
keywords: Apoptosis; blood–brain barrier; doxorubicin; poly(butylcyanoacrylate) nanoparticles; polysorbate 80