Drug-loaded carbon nanohorns: Adsorption and release of dexamethasone in vitro
Drug-loaded carbon nanohorns: Adsorption and release of dexamethasone in vitro
复制标题
DOI：
10.1021/mp049928e
复制
发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Shiba, Kiyotaka
中科院分区：
文献类型：
--
作者：
Muralkami, Tatsuya;Ajima, Kumiko;Shiba, Kiyotaka
单壁碳纳米角（SWNHs）是近年来发现的石墨管球形纳米聚集体。SWNHs独特的物理化学性质，包括它们的大表面积，表明它们可能作为药物输送系统的载体。在这里，我们研究了生长的SWNHs及其氧化形式oxSWNHs对抗炎糖皮质激素地塞米松（DEX）的体外结合和释放。用[H-3]-DEX进行吸附分析，测定在0.5 mg/mL DEX溶液中，oxSWNHs对DEX的吸附量为每克oxSWNHs吸附200 mg，约为生长SWNHs的6倍。吸附动力学表明，氧化SWNHs对DEX的亲和力高于生长SWNHs。在1200℃H-2条件下处理oxSWNHs，虽然去除了oxSWNHs上的含氧官能团，但并未降低oxSWNHs对DEX的高亲和力，说明含氧官能团对其亲和力贡献不大。DEX- oxswnh配合物在37℃下持续释放到磷酸盐缓冲盐水（pH 7.4）中，并快速双相释放到培养基中。通过在小鼠骨髓基质ST2细胞中激活糖皮质激素反应元件驱动的转录和在小鼠成骨细胞MC3T3-E1细胞中诱导碱性磷酸酶，证实了释放的DEX形式的生物完整性。值得注意的是，SWNHs的合成不需要金属催化剂，其毒性在临床使用中可能会成为问题，并且在我们的条件下，在oxSWNHs存在下培养的细胞中没有观察到细胞毒性。综上所述，这些观察结果突出了SWNHs在药物输送系统中的潜在效用。
Single-wall carbon nanohorns (SWNHs) are recently discovered nanostructured spherical aggregates of graphitic tubes. The unique physicochemical properties of SWNHs, including their large surface area, suggest their possible utility as carriers in drug delivery systems. Here we investigated the in vitro binding and release of the anti inflammatory glucocorticoid dexamethasone (DEX) by as-grown SWNHs and their oxidized form, oxSWNHs. Adsorption analyses using [H-3]-DEX determined the amount of DEX adsorbed by oxSWNHs to be 200 mg for each gram of oxSWNHs in 0.5 mg/mL of DEX solution, which was approximately 6 times larger than that obtained for as-grown SWNHs. Adsorption kinetics indicated that oxSWNHs had higher affinity for DEX than as-grown SWNHs. Treatment of oxSWNHs at 1200 degrees C under H-2, which removed the oxygen-containing functional groups on oxSWNHs, did not diminish the high affinity for DEX, suggesting that oxygen-containing functional groups have little contribution for the affinity. DEX-oxSWNH complexes exhibited sustained release of DEX into phosphate-buffered saline (pH 7.4) at 37 degrees C and more rapid biphasic release into culture medium. The biological integrity of the released DEX form was confirmed by activation of glucocorticoid response element-driven transcription in mouse bone marrow stromal ST2 cells and induction of alkaline phosphatase in mouse osteoblastic MC3T3-E1 cells. Notably, synthesis of SWNHs does not require a metal catalyst, the toxicity of which could become problematical in clinical use, and no cytotoxicity was observed in cells cultured in the presence of oxSWNHs under our conditions. Taken together, these observations highlight the potential utility of SWNHs in drug delivery systems.