TY - JOUR
T1 - In vivo evaluation of safety of nanoporous silicon carriers following single and multiple dose intravenous administrations in mice
AU - Tanaka, T.
AU - Godin, B.
AU - Bhavane, R.
AU - Nieves-Alicea, R.
AU - Gu, J.
AU - Liu, X.
AU - Chiappini, C.
AU - Fakhoury, J. R.
AU - Amra, S.
AU - Ewing, A.
AU - Li, Q.
AU - Fidler, I. J.
AU - Ferrari, M.
N1 - Funding Information:
Lou Brousseau is gratefully recognized for the insightful discussion of the manuscript. The authors acknowledge a financial support from the following sources: NIH U54CA143837, DODW81XWH-09-1-0212, DODW81XWH-07-2-0101; NIH RO1CA128797, NIH-R33 CA122864 and State of Texas Emerging Technology Fund.
PY - 2010/12/15
Y1 - 2010/12/15
N2 - 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.
AB - 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.
KW - Biocompatibility
KW - Multistage carrier
KW - Nanoporous silicon
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U2 - 10.1016/j.ijpharm.2010.09.015
DO - 10.1016/j.ijpharm.2010.09.015
M3 - Article
C2 - 20883755
AN - SCOPUS:78349311319
SN - 0378-5173
VL - 402
SP - 190
EP - 197
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -