In vivo evaluation of safety of nanoporous silicon carriers following single and multiple dose intravenous administrations in mice

T. Tanaka, B. Godin, R. Bhavane, R. Nieves-Alicea, J. Gu, X. Liu, C. Chiappini, J. R. Fakhoury, S. Amra, A. Ewing, Q. Li, I. J. Fidler, M. Ferrari

Research output: Contribution to journalArticle

75 Scopus citations

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 (107, 108, 5×108 S1MP/animal) and subchronic multiple dose (108 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 108 negatively charged S1MP, 108 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.

Original languageEnglish (US)
Pages (from-to)190-197
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume402
Issue number1-2
DOIs
StatePublished - Dec 15 2010

Keywords

  • Biocompatibility
  • Multistage carrier
  • Nanoporous silicon

ASJC Scopus subject areas

  • Pharmaceutical Science

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