皮肤是人类的第一个屏障,每天暴露于广泛的物理和化学试剂,这会增加活性氧(ROS)并导致局部疾病的形成。抗氧化分子,例如苯并[k,l]黄吨木酚素(BXL),是消除或最小化ROS影响的理想候选者。在这里,我们旨在配制负载BXL的固体脂质纳米粒(SLN-BXL),以提高生物利用度和与皮肤的相互作用,并与无药情况相比,研究HFF-1中对细胞内ROS产生的保护作用。SLN-BXL使用PIT/超声处理方法配制,然后进行物理化学表征,即,平均大小,zeta电位(ZP),多分散指数(PDI),封装效率(%EE),热致行为,以及与生物膜模型的相互作用。结果显示平均尺寸约为200nm,PDI为0.2,zeta电位约为-28mV,值在三个月内几乎不变,而EE%约为70%。此外,SLN-BXL能够与生物膜模型深度相互作用,并在轻度疏水基质中实现双重作用释放;体外实验的结果证实SLN-BXL是细胞安全的并且能够减弱IL-2诱导的高ROS水平。总之,根据我们的发现,该制剂可被提议作为针对由ROS水平增加引起的皮肤疾病的预防性治疗的候选物。
Skin is the first human barrier that is daily exposed to a broad spectrum of physical and chemical agents, which can increase reactive oxygen species (ROS) and lead to the formation of topical disorders. Antioxidant molecules, such as benzo[k,l]xanthene lignans (BXL), are ideal candidates to eliminate or minimize the effects of ROS. Herein, we aimed to formulate BXL-loaded solid lipid nanoparticles (SLN-BXL) to improve the bioavailability and interaction with the skin, and also to investigate the protective impact against intracellular ROS generation in HFF-1 in comparison with the drug-free situation. SLN-BXL were formulated using the PIT/ultrasonication method, and then were subjected to physicochemical characterizations, i.e., average size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (%EE), thermotropic behavior, and interaction with a biomembrane model. The results show a mean size around 200 nm, PDI of 0.2, and zeta potential of about -28 mV, with values almost unchanged over a period of three months, while the EE% is ≈70%. Moreover, SLN-BXL are able to deeply interact with the biomembrane model, and to achieve a double-action release in mildly hydrophobic matrices; the results of the in vitro experiments confirm that SLN-BXL are cell-safe and capable of attenuating the IL-2-induced high ROS levels. In conclusion, based on our findings, the formulation can be proposed as a candidate for a preventive remedy against skin disorders induced by increased levels of ROS.