Cytotoxicity, in Vivo Skin Irritation and Acute Systemic Toxicity of the Mesoporous Magnesium Carbonate Upsalite®

S. Frykstrand, J. Forsgren, Peng Zhang, M. Strømme, N. Ferraz
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引用次数: 20

Abstract

Upsalite® is a mesoporous magnesium carbonate synthesized without using surfactants and therefore highly attractive from environmental and production economy points of view. The material has recently been suggested as drug delivery vehicle and as topical bacteriostatic agent. In order to continue exploring these and other bio-related applications of the material, primary biocompatibility studies are needed. Herein we present the first in vivo acute systemic toxicity and skin irritation analyses as well as in vitro cytotoxicity evaluations of Upsalite®. The material was found to be non-toxic for human dermal fibroblasts cells up to a concentration of 1000 μg/ml and 48 h exposure in contrast to the mesoporous silica material SBA-15, used as reference, which significantly affected cell viability at particle concentration of 500 and 1000 μg/ml after the same exposure time. Topical application of Upsalite® resulted in negligible cutaneous reactions in a rabbit skin irritation model and no evidence of significant systemic toxicity was found when saline extracts of Upsalite® were injected in mice. Injection of sesame oil extract, however, resulted in transient weight loss, most likely due to injection of particles, and not toxic leachables. The presented results form the basis for future development of Upsalite® and similar mesoporous materials in biomedical applications and further toxicity as well as biocompatibility studies should be directed towards specific areas of use.
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介孔碳酸镁的细胞毒性、体内皮肤刺激和急性全身毒性
Upsalite®是一种不使用表面活性剂合成的介孔碳酸镁,因此从环境和生产经济的角度来看非常有吸引力。该材料最近被建议作为药物传递载体和局部抑菌剂。为了继续探索这种材料的这些和其他生物相关应用,需要进行初步的生物相容性研究。在此,我们提出了Upsalite®的第一个体内急性全身毒性和皮肤刺激分析以及体外细胞毒性评估。与以介孔二氧化硅材料SBA-15为对照,在500和1000 μg/ml的颗粒浓度下,同样暴露时间后,SBA-15对人真皮成纤维细胞的活性有显著影响。在兔皮肤刺激模型中,局部应用Upsalite®导致可忽略的皮肤反应,而在小鼠中注射Upsalite®的生理盐水提取物时,没有发现明显的全身毒性证据。然而,注射芝麻油提取物会导致短暂的体重减轻,这很可能是由于注射了颗粒,而不是有毒的浸出物。所提出的结果为Upsalite®和类似的介孔材料在生物医学应用中的未来发展奠定了基础,进一步的毒性和生物相容性研究应该针对特定的使用领域。
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