Abedin Zadeh Maria, Alany Raid G, Satarian Leila, Shavandi Amin, Abdullah Almousa Mohamed, Brocchini Steve, Khoder Mouhamad
Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames KT1 2EE, UK.
UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
Pharmaceutics. 2023 Apr 24;15(5):1330. doi: 10.3390/pharmaceutics15051330.
There are limited treatments currently available for retinal diseases such as age-related macular degeneration (AMD). Cell-based therapy holds great promise in treating these degenerative diseases. Three-dimensional (3D) polymeric scaffolds have gained attention for tissue restoration by mimicking the native extracellular matrix (ECM). The scaffolds can deliver therapeutic agents to the retina, potentially overcoming current treatment limitations and minimizing secondary complications. In the present study, 3D scaffolds made up of alginate and bovine serum albumin (BSA) containing fenofibrate (FNB) were prepared by freeze-drying technique. The incorporation of BSA enhanced the scaffold porosity due to its foamability, and the Maillard reaction increased crosslinking degree between ALG with BSA resulting in a robust scaffold with thicker pore walls with a compression modulus of 13.08 KPa suitable for retinal regeneration. Compared with ALG and ALG-BSA physical mixture scaffolds, ALG-BSA conjugated scaffolds had higher FNB loading capacity, slower release of FNB in the simulated vitreous humour and less swelling in water and buffers, and better cell viability and distribution when tested with ARPE-19 cells. These results suggest that ALG-BSA MR conjugate scaffolds may be a promising option for implantable scaffolds for drug delivery and retinal disease treatment.
目前针对年龄相关性黄斑变性（AMD）等视网膜疾病的治疗方法有限。基于细胞的疗法在治疗这些退行性疾病方面具有巨大潜力。三维（3D）聚合物支架通过模拟天然细胞外基质（ECM）在组织修复方面受到关注。这种支架可以将治疗剂递送至视网膜，有可能克服当前治疗的局限性并将继发性并发症降至最低。在本研究中，通过冷冻干燥技术制备了由含有非诺贝特（FNB）的藻酸盐和牛血清白蛋白（BSA）组成的3D支架。BSA的加入因其发泡性提高了支架孔隙率，美拉德反应增加了ALG与BSA之间的交联度，从而形成了一种坚固的支架，其孔壁更厚，压缩模量为13.08 KPa，适合视网膜再生。与ALG和ALG-BSA物理混合支架相比，ALG-BSA共轭支架具有更高的FNB负载能力，在模拟玻璃体液中FNB释放更慢，在水和缓冲液中肿胀更小，并且在用ARPE-19细胞测试时具有更好的细胞活力和分布。这些结果表明，ALG-BSA MR共轭支架可能是用于药物递送和视网膜疾病治疗的可植入支架的一个有前景的选择。
