Krstić Luna, Vallejo Reinaldo, Rodriguez-Rojo Soraya, González-García María J, Arias F Javier, Girotti Alessandra, Diebold Yolanda
Instituto de Oftalmobiología Aplicada (IOBA), Universidad de Valladolid, Paseo Belén 17, 47011 Valladolid, Spain.
BioEcoUVa, Research Institute on Bioeconomy, PressTech Group, University of Valladolid, Department of Chemical Engineering and Environmental Technology, Escuela de Ingenierías Industriales, Sede Mergelina, 47011 Valladolid, Spain; Smart Devices for NanoMedicine Group, University of Valladolid, LUCIA Building, Paseo Belén 19, 47011 Valladolid, Spain.
Int J Pharm. 2025 Jun 10;678:125691. doi: 10.1016/j.ijpharm.2025.125691. Epub 2025 May 7.
The present study is centred on the development of a therapeutic strategy for Dry Eye Disease (DED), and all experimental models, formulation designs, and outcome measures have been specifically tailored to address this pathology. Elastin-like polymers (ELPs) are emerging as a groundbreaking nanobiomaterial for advanced drug delivery systems, thanks to their biomimetic, adaptable, and stimuli-responsive properties. Embracing sustainability, we employed supercritical CO (scCO) as an eco-friendly alternative to organic solvents to develop an innovative ELP-based particulate system. This system, designed for topical ophthalmic applications, incorporates two antioxidant and anti-inflammatory polyphenolic compounds, quercetin (QUE) and resveratrol (RSV), through a one-step supercritical antisolvent (SAS) process. Post-SAS process, we achieved solid microparticles loaded with QUE, RSV, or a combination of both. Remarkably, these microparticles transform into nanoparticles (NPs) with an average size of 56.7 ± 1.0 to 61.5 ± 2.6 nm when placed in solution at physiological temperature. This transformation leverages the stimulus-responsive nature of ELP, ensuring sustained polyphenol release. Our ELP-based formulations demonstrate exceptional biocompatibility with Human Corneal Epithelial cells (HCEs) and exhibit outstanding intracellular scavenging activity against reactive oxygen species (ROS). To track cellular uptake, we developed particles with a two fluorescent tags. This system successfully delivered the fluorescent payload to cells and efficiently targeted the corneal epithelium in ex vivo porcine eye globes, showcasing time-dependent delivery.
本研究聚焦于干眼症（DED）治疗策略的开发，所有实验模型、制剂设计和结果测量均专门针对该病症进行了定制。弹性蛋白样聚合物（ELP）因其仿生、适应性和刺激响应特性，正成为先进药物递送系统中一种开创性的纳米生物材料。为了实现可持续发展，我们采用超临界CO₂（scCO₂）作为有机溶剂的环保替代品，来开发一种基于ELP的创新颗粒系统。该系统专为局部眼科应用设计，通过一步超临界抗溶剂（SAS）工艺，将两种抗氧化和抗炎多酚化合物槲皮素（QUE）和白藜芦醇（RSV）纳入其中。经过SAS工艺后，我们获得了负载QUE、RSV或两者组合的固体微粒。值得注意的是，当这些微粒置于生理温度的溶液中时，它们会转变为平均尺寸为56.7±1.0至61.5±2.6 nm的纳米颗粒（NP）。这种转变利用了ELP的刺激响应特性，确保多酚的持续释放。我们基于ELP的制剂与人类角膜上皮细胞（HCE）表现出卓越的生物相容性，并对活性氧（ROS）展现出出色的细胞内清除活性。为了追踪细胞摄取情况，我们开发了带有两种荧光标签的颗粒。该系统成功地将荧光负载递送至细胞，并在离体猪眼球中有效地靶向角膜上皮，展示了时间依赖性递送。
