title: In vivo evaluation of safety of nanoporous silicon carriers following single and multiple dose intravenous administrations in mice.
abstract: Porous silicon (pSi) is being extensively studied as an emerging material for use in biomedical applications, including drug delivery, based on the biodegradability and versatile chemical and biophysical properties. We have recently introduced multistage nanoporous silicon microparticles (S1MP) designed as a cargo for nanocarrier drug delivery to enable the loaded therapeutics and diagnostics to sequentially overcome the biological barriers in order to reach their target. In this first report on biocompatibility of intravenously administered pSi structures, we examined the tolerability of negatively (-32.5±3.1mV) and positively (8.7±2.5mV) charged S1MP in acute single dose (10(7), 10(8), 5×10(8) S1MP/animal) and subchronic multiple dose (10(8) S1MP/animal/week for 4 weeks) administration schedules. Our data demonstrate that S1MP did not change plasma levels of renal (BUN and creatinine) and hepatic (LDH) biomarkers as well as 23 plasma cytokines. LDH plasma levels of 145.2±23.6, 115.4±29.1 vs. 127.0±10.4; and 155.8±38.4, 135.5±52.3 vs. 178.4±74.6 were detected in mice treated with 10(8) negatively charged S1MP, 10(8) positively charged S1MP vs. saline control in single and multiple dose schedules, respectively. The S1MPs did not alter LDH levels in liver and spleen, nor lead to infiltration of leukocytes into the liver, spleen, kidney, lung, brain, heart, and thyroid. Collectively, these data provide evidence of a safe intravenous administration of S1MPs as a drug delivery carrier.
authors.affiliation: Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center, 1825 Pressler, Suite 537, Houston, TX 77030, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: B
authors.initials: B
authors.lastname: Godin
authors.forename: R
authors.initials: R
authors.lastname: Bhavane
authors.forename: R
authors.initials: R
authors.lastname: Nieves-Alicea
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Chiappini
authors.forename: J R
authors.initials: JR
authors.lastname: Fakhoury
authors.forename: S
authors.initials: S
authors.lastname: Amra
authors.forename: A
authors.initials: A
authors.lastname: Ewing
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: I J
authors.initials: IJ
authors.lastname: Fidler
authors.forename: M
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D016503:Drug Delivery Systems; D005260:Female; D007275:Injections, Intravenous; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008863:Microspheres; D058608:Nanopores; D012825:Silicon / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D007770:L-Lactate Dehydrogenase; D012825:Silicon