Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 6500, Thailand.
Centre of excellence in Fungal Research and Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 6500, Thailand.
Curr Drug Deliv. 2019;16(7):645-653. doi: 10.2174/1567201816666190729145223.
BACKGROUND: Amphotericin B (AmB) is important for the treatment of systemic fungal infections. Nowadays, only intravenous administration (IV) of AmB has been available due to its low aqueous solubility. Two forms of AmB are available. The first is Fungizone®, a mixture of AmB and sodium deoxcycholate that produces severe nephrotoxicity. The second are lipid-based formulations that reduce nephrotoxicity, but they are costly and require higher dose than Fungizone®. Thus, a cheaper delivery system with reduced AmB toxicity is required. OBJECTIVE: To develop and characterize AmB loaded-nanostructured lipid carriers (AmB-loaded NLCs) for IV administration to reduce AmB toxicity. METHODS: AmB-loaded NLCs with different solid lipids were prepared by the high-pressure homogenization technique. Their physicochemical properties and the drug release profile were examined. The molecular structure of AmB, antifungal and hemolysis activities of developed AmB-loaded NLCs were also evaluated. RESULTS: AmB-loaded NLCs ~110 to ~140 nm in diameter were successfully produced with a zeta potential of ~-19 mV and entrapment efficiency of ~75%. In vitro release showed fast release characteristics. AmB-loaded NLCs could reduce the AmB molecular aggregation as evident from the absorbance ratio of the first to the fourth peak showing a partial aggregation of AmB. This result suggested that AmB-loaded NLCs could offer less nephrotoxicity compared to Fungizone®. In vitro antifungal activity of AmB-loaded NLCs showed a minimum inhibitory concentration of 0.25 µgmL-1. CONCLUSION: AmB-loaded NLCs present high potential carriers for effective IV treatment with prolonged circulation time and reduced toxicity.
背景：两性霉素 B（AmB）对治疗系统性真菌感染非常重要。由于其水溶性低，目前仅可通过静脉注射（IV）使用。两性霉素 B 有两种剂型。第一种是两性霉素 B 与脱氧胆酸钠的混合物 Fungizone®，它会导致严重的肾毒性。第二种是基于脂质的制剂，可降低肾毒性，但价格昂贵，所需剂量高于 Fungizone®。因此，需要一种毒性更低、更廉价的输送系统。
目的：开发并表征用于 IV 给药的两性霉素 B 载纳米结构化脂质载体（AmB-loaded NLCs），以降低两性霉素 B 的毒性。
方法：采用高压匀质技术制备了不同固体脂质的两性霉素 B 载纳米结构化脂质载体。考察了它们的理化性质和药物释放曲线。还评估了 AmB 的分子结构、开发的两性霉素 B 载纳米结构化脂质载体的抗真菌和溶血活性。
结果：成功制备了直径为 110 至 140nm、zeta 电位约为-19mV、包封效率约为 75%的两性霉素 B 载纳米结构化脂质载体。体外释放显示出快速释放的特点。AmB-loaded NLCs 可以减少两性霉素 B 的分子聚集，这从第一到第四峰的吸光度比值可以看出，表明两性霉素 B 部分聚集。这一结果表明，与 Fungizone®相比，AmB-loaded NLCs 的肾毒性可能更低。AmB-loaded NLCs 的体外抗真菌活性显示最低抑菌浓度为 0.25µgmL-1。
结论：两性霉素 B 载纳米结构化脂质载体具有很大的潜力，可作为有效的 IV 治疗载体，具有延长的循环时间和降低的毒性。
Pharmaceuticals (Basel). 2020-6-11
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