Zingale Elide, Weaver Edward, Bertelli Pietro Maria, Lengyel Imre, Pignatello Rosario, Lamprou Dimitrios A
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6, 95125 Catania, Italy.
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
Int J Pharm. 2024 Nov 15;665:124700. doi: 10.1016/j.ijpharm.2024.124700. Epub 2024 Sep 13.
Treating diabetic retinopathy (DR) effectively is challenging, aiming for high efficacy with minimal discomfort. While intravitreal injection is the current standard, it has several disadvantages. Implantable systems offer an alternative, less invasive, with long-lasting effects drug delivery system (DDS). The current study aims to develop a soft, minimally invasive, biodegradable, and bioadhesive material-based hydrogel scaffold to prevent common issues with implants. A grid-shaped scaffold was created using coaxial 3D printing (3DP) to extrude two bioinks in a single filament. The scaffold comprises an inner core of curcumin-loaded liposomes (CUR-LPs) that prepared by microfluidics (MFs) embedded in a hydrogel of hydroxyethyl cellulose (HEC), and an outer layer of hyaluronic acid-chitosan matrix with free resveratrol (RSV), delivering two Sirt1 agonists synergistically activating Sirt1 downregulated in DR. Optimized liposomes, prepared via MFs, exhibit suitable properties for retinal delivery in terms of size (<200 nm), polydispersity index (PDI) (<0.3), neutral zeta potential (ZP), encapsulation efficiency (∼97 %), and stability up to 4 weeks. Mechanical studies confirm scaffold elasticity for easy implantation. The release profiles show sustained release of both molecules, with different patterns related to different localization of the molecules. RSV released initially after 30 min with a total release more than 90 % at 336 h. CUR release starts after 24 h with only 4.78 % of CUR released before and gradually released thanks to its internal localization in the scaffold. Liposomes and hydrogels can generate dual drug-loaded 3D structures with sustained release. Microscopic analysis confirms optimal distribution of liposomes within the hydrogel scaffold. The latter resulted compatible in vitro with human retinal microvascular endothelial cells up to 72 h of exposition. The hydrogel scaffold, composed of hyaluronic acid and chitosan, shows promise for prolonged treatment and minimally invasive surgery.
有效治疗糖尿病视网膜病变（DR）具有挑战性，目标是在不适最小化的情况下实现高效治疗。虽然玻璃体内注射是当前的标准治疗方法，但它有几个缺点。可植入系统提供了一种侵入性较小、具有长效作用的药物递送系统（DDS）作为替代方案。当前的研究旨在开发一种基于柔软、微创、可生物降解且具有生物粘附性材料的水凝胶支架，以解决植入物的常见问题。使用同轴3D打印（3DP）创建了一种网格状支架，以便在单丝中挤出两种生物墨水。该支架包括由微流控技术（MFs）制备的负载姜黄素的脂质体（CUR-LPs）的内核，其嵌入羟乙基纤维素（HEC）水凝胶中，以及含有游离白藜芦醇（RSV）的透明质酸-壳聚糖基质外层，协同递送两种Sirt1激动剂，激活DR中下调的Sirt1。通过MFs制备的优化脂质体在尺寸（<200nm）、多分散指数（PDI）（<0.3）、中性zeta电位（ZP）、包封效率（约97%）以及长达4周的稳定性方面表现出适合视网膜递送的特性。力学研究证实了支架的弹性，便于植入。释放曲线显示两种分子均持续释放，但与分子的不同定位相关的释放模式不同。RSV在30分钟后开始释放，在336小时时总释放量超过90%。CUR在24小时后开始释放，在此之前仅释放4.78%，由于其在支架内的内部定位而逐渐释放。脂质体和水凝胶可以生成具有持续释放功能的双载药3D结构。显微镜分析证实了脂质体在水凝胶支架内的最佳分布。后者在体外与人视网膜微血管内皮细胞共培养72小时后显示出相容性。由透明质酸和壳聚糖组成的水凝胶支架在延长治疗和微创手术方面显示出前景。
