Alves da Silva Bruna Terra, Silva Lautenschlager Sueli de Oliveira, Nakamura Celso Vataru, Ximenes Valdecir Farias, Ogawa Yu, Michel Raphaël, Auzély-Velty Rachel
Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil.
Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil; Department of Basic Health Sciences, Maringa State University (UEM), Maringá, Paraná 87020900, Brazil.
Int J Pharm. 2025 Jan 25;669:125010. doi: 10.1016/j.ijpharm.2024.125010. Epub 2024 Nov 30.
Exposure of the skin to ultraviolet (UV) radiation is associated with many pathological conditions such as premature aging and skin cancer. Furthermore, members of Nicotinamide Adenine Dinucleotide Phosphate-oxidase (NADPH oxidase or NOX) enzyme family can produce UV-induced reactive oxygen species (ROS), even after cessation of radiation exposure. The caffeic acid-phthalimide (CF) compound is a potent antioxidant, which reduces the generation of ROS. However, its high lipophilicity may hamper its permeation through the skin. Solid lipid nanoparticles (SLNs) can ensure close contact and increase the amount of drug absorbed into the skin. The present work aims to develop and optimize SLNs containing CF to achieve enhanced skin photoprotection along with antioxidant and anti-aging effects. SLNs were prepared by the hot homogenization method using Compritol 888 ATO as lipid matrix, and Tween 80 and Pluronic® F-127 as surfactants to stabilize the nanoparticle dispersion. The particles had high stability for at least 30 days. Physicochemical characterizations of the selected SLNs formulations showed sizes in the range 150-180 nm, polydispersity index (PDI) of 0.2, and a negative zeta potential (≅ -25 mV). The SLNs had high CF entrapment efficiency (96-97 %) and showed a controlled drug-release profile. The in vitro study revealed low cytotoxic properties of CF-loaded SLNs towards fibroblasts and a photoprotective effect, reflected from the increased viability of UVB-irradiated fibroblasts treated with CF-SLNs. Moreover, the CF-SLNs induced fibroblast migration and closure, showing that these nanosystems offer not only biological photoprotection, but also stimulate wound healing.
皮肤暴露于紫外线（UV）辐射会引发许多病理状况，如过早衰老和皮肤癌。此外，烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶或NOX）家族的成员即使在辐射暴露停止后，仍可产生紫外线诱导的活性氧（ROS）。咖啡酸邻苯二甲酰亚胺（CF）化合物是一种有效的抗氧化剂，可减少ROS的产生。然而，其高亲脂性可能会阻碍其透过皮肤。固体脂质纳米粒（SLNs）可确保紧密接触并增加药物透皮吸收量。本研究旨在开发并优化含CF的SLNs，以实现增强的皮肤光保护以及抗氧化和抗老化效果。采用热均质法，以Compritol 888 ATO为脂质基质，吐温80和泊洛沙姆F-127为表面活性剂制备SLNs，以稳定纳米颗粒分散体。这些颗粒至少30天具有高稳定性。所选SLNs制剂的物理化学表征显示，其粒径范围为150 - 180 nm，多分散指数（PDI）为0.2，zeta电位为负（约 -25 mV）。SLNs具有高CF包封率（96 - 97%），并呈现出可控的药物释放曲线。体外研究表明，负载CF的SLNs对成纤维细胞具有低细胞毒性，并具有光保护作用，这从用CF - SLNs处理的经UVB照射的成纤维细胞活力增加可以看出。此外，CF - SLNs诱导成纤维细胞迁移和闭合，表明这些纳米系统不仅提供生物光保护，还能刺激伤口愈合。
