In vivo evaluation of safety of nanoporous silicon carriers following single and multiple dose intravenous administrations in mice
| Autor: | Ciro Chiappini, René Nieves-Alicea, Jianhua Gu, Rohan Bhavane, Biana Godin, Isaiah J Fidler, Mauro Ferrari, Q. Li, Xinming Liu, A. Ewing, S. Amra, Jean R. Fakhoury, Takemi Tanaka |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Silicon Pharmaceutical Science Spleen Pharmacology Drug Administration Schedule Article Mice Nanopores Drug Delivery Systems In vivo Toxicity Tests Animals Medicine Drug Carriers Kidney Dose-Response Relationship Drug L-Lactate Dehydrogenase business.industry Microspheres medicine.anatomical_structure Tolerability Injections Intravenous Toxicity Drug delivery Cytokines Female Nanocarriers business Drug carrier |
| Zdroj: | International Journal of Pharmaceutics. 402:190-197 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2010.09.015 |
| Popis: | 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 ± 3.1 mV) and positively (8.7 ± 2.5 mV) 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. |
| Databáze: | OpenAIRE |
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