Laboratório de Tecnologia Farmacêutica, Programa de Pós-graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, 97105-900, Brazil.
Centro Universitário Franciscano, Santa Maria, Brazil.
AAPS PharmSciTech. 2017 Nov;18(8):3236-3246. doi: 10.1208/s12249-017-0810-5. Epub 2017 Jun 2.
Silibinin (SB) and pomegranate oil (PO) present therapeutic potential due to antioxidant activity, but the biological performance of both bioactives is limited by their low aqueous solubility. To overcome this issue, the aim of the present investigation was to develop nanocapsule suspensions with PO as oil core for SB encapsulation, as well as assess their toxicity in vitro and radical scavenging activity. The nanocapsule suspensions were prepared by interfacial deposition of preformed polymer method. SB-loaded PO-based nanocapsules (SBNC) showed an average diameter of 157 ± 3 nm, homogenous size distribution, zeta potential of -14.1 ± 1.7 mV, pH of 5.6 ± 0.4 and SB content close to 100%. Similar results were obtained for the unloaded formulation (PONC). The nanocapsules controlled SB release at least 10 times as compared with free SB in methanolic solution. The SBNC scavenging capacity in vitro was statistically higher than free SB (p < 0.05). Cell viability in monocytes and lymphocytes was kept around 100% in the treatments with SBNC and PONC, while the SB and the PO caused a decrease around 30% at 50 μM (SB) and 724 μg/mL (PO). Protein carbonyls and DNA damage were minimized by SB and PO nanoencapsulation. Lipid peroxidation occurred in nanocapsule treatments regardless of the SB presence, which may be attributed to PO acting as substrate in reaction. The free compounds also caused lipid peroxidation. The results show that SBNC and PONC presented adequate physicochemical characteristics and low toxicity against human blood cells. Thereby, this novel nanocarrier may be a promising formulation for therapeutic applications.
水飞蓟宾（SB）和石榴籽油（PO）具有抗氧化活性，因此具有治疗潜力，但由于其低水溶性，这两种生物活性物质的生物学性能受到限制。为了克服这个问题，本研究的目的是开发以 PO 为油芯的纳米胶囊混悬液，用于 SB 包封，并评估其体外毒性和自由基清除活性。纳米胶囊混悬液通过界面沉积法制备。载有 SB 的 PO 基纳米胶囊（SBNC）的平均粒径为 157±3nm，粒径分布均匀，Zeta 电位为-14.1±1.7mV，pH 值为 5.6±0.4，SB 含量接近 100%。未负载配方（PONC）也得到了类似的结果。与甲醇溶液中的游离 SB 相比，纳米胶囊至少控制了 10 倍的 SB 释放。体外 SBNC 的清除能力明显高于游离 SB（p<0.05）。SBNC 和 PONC 处理的单核细胞和淋巴细胞的细胞活力保持在 100%左右，而 SB 和 PO 在 50μM（SB）和 724μg/mL（PO）时导致细胞活力下降约 30%。纳米胶囊包封 SB 和 PO 可最大限度地减少蛋白质羰基和 DNA 损伤。脂质过氧化发生在纳米胶囊处理中，无论 SB 是否存在，这可能归因于 PO 作为反应的底物。游离化合物也会引起脂质过氧化。结果表明，SBNC 和 PONC 具有适当的物理化学特性和低毒性，对人血红细胞无毒性。因此，这种新型纳米载体可能是一种有前途的治疗应用制剂。
