Montenegro Lucia, Panico Anna Maria, Santagati Ludovica Maria, Siciliano Edy Angela, Intagliata Sebastiano, Modica Maria N
Department of Drug Sciences, University of Catania, 95125 Catania, Italy.
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA.
Nanomaterials (Basel). 2018 Dec 29;9(1):43. doi: 10.3390/nano9010043.
Idebenone (IDE), a strong antioxidant widely investigated for the treatment of neurodegenerative diseases and skin disorders, shows low oral and topical bioavailability due to its unfavorable physico-chemical properties. In this work, to improve IDE topical effectiveness, we explored a two-steps approach: (1) we synthesized an IDE ester (IDEPCA) with pyroglutamic acid, a molecule whose hydrating effects are well known; (2) we loaded IDEPCA into solid lipid nanocarriers (SLN). We evaluated in vitro antioxidant and anti-glycation activity and in vivo hydrating effects after topical application in human volunteers from gel vehicles of IDEPCA SLN in comparison to IDE SLN. All SLN showed good technological properties (mean particle size < 25 nm, polydispersity index < 0.300, good stability). The oxygen radical absorbance capacity assay showed that IDEPCA SLN and IDE SLN had similar antioxidant activity while IDEPCA SLN were more effective in the in vitro NO scavenging assay. Both IDEPCA and IDE SLN showed the same effectiveness in inhibiting the formation of advanced glycation end products. In vivo experiments pointed out a better hydrating effect of IDEPCA SLN in comparison to IDE SLN. These results suggest that the investigated approach could be a promising strategy to obtain topical formulations with increased hydrating effects.
艾地苯醌（IDE）是一种因具有抗氧化特性而被广泛研究用于治疗神经退行性疾病和皮肤疾病的药物，但其不良的物理化学性质导致其口服和局部生物利用度较低。在这项工作中，为了提高IDE的局部疗效，我们探索了一种两步法：（1）我们合成了一种艾地苯醌酯（IDEPCA），它是艾地苯醌与焦谷氨酸形成的酯，焦谷氨酸的保湿作用是众所周知的；（2）我们将IDEPCA负载到固体脂质纳米载体（SLN）中。我们评估了IDEPCA SLN凝胶载体与IDE SLN相比，在人体志愿者局部应用后的体外抗氧化和抗糖化活性以及体内保湿效果。所有SLN均表现出良好的技术性能（平均粒径<25nm，多分散指数<0.300，稳定性良好）。氧自由基吸收能力测定表明，IDEPCA SLN和IDE SLN具有相似的抗氧化活性，而IDEPCA SLN在体外NO清除试验中更有效。IDEPCA和IDE SLN在抑制晚期糖基化终产物形成方面表现出相同的效果。体内实验表明，与IDE SLN相比，IDEPCA SLN具有更好的保湿效果。这些结果表明，所研究的方法可能是一种有前景的策略，以获得具有增强保湿效果的局部制剂。
