Alshammari Rehab A, Aleanizy Fadilah S, Aldarwesh Amal, Alqahtani Fulwah Y, Mahdi Wael A, Alquadeib Bushra, Alqahtani Qamraa H, Haq Nazrul, Shakeel Faiyaz, Abdelhady Hosam G, Alsarra Ibrahim A
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Pharmaceutics. 2022 Jul 11;14(7):1444. doi: 10.3390/pharmaceutics14071444.
Ruboxistaurin (RBX) is an anti-vascular endothelial growth factor (anti-VEGF) agent that is used in the treatment of diabetic retinopathy and is mainly given intravitreally. To provide a safe and effective method for RBX administration, this study was designed to develop RBX nanoparticles using polyamidoamine (PAMAM) dendrimer generation 5 for the treatment of diabetic retinopathy. Drug loading efficiency, and in vitro release of proposed complexes of RBX: PAMAM dendrimers were determined and the complexation ratio that showed the highest possible loading efficiency was selected. The drug loading efficiency (%) of 1:1, 2.5:1, and 5:1 complexes was 89.2%, 96.4%, and 97.6%, respectively. Loading capacities of 1:1, 2.5:1, and 5:1 complexes were 1.6%, 4.0%, and 7.2% respectively. In comparison, the 5:1 complex showed the best results in the aforementioned measurements. The in vitro release studies showed that in 8 h, the RBX release from 1:1, 2.5:1, and 5:1 complexes was 37.5%, 35.9%, and 77.0%, respectively. In particular, 5:1 complex showed the highest drug release. In addition, particle size measurements showed that the diameter of empty PAMAM dendrimers was 214.9 ± 8.5 nm, whereas the diameters of loaded PAMAM dendrimers in 1:1, 2.5:1, 5:1 complexes were found to be 461.0 ± 6.4, 482.4 ± 12.5, and 420.0 ± 7.1 nm, respectively. Polydispersity index (PDI) showed that there were no significant changes in the PDI between the free and loaded PAMAM dendrimers. The zeta potential measurements showed that the free and loaded nanoparticles possessed neutral charges due to the presence of anionic and cationic terminal structures. Furthermore, the safety of this formulation was apparent on the viability of the MIO-M1 cell lines. This nanoformulation will improve the therapeutic outcomes of anti-VEGF therapy and the bioavailability of RBX to prevent vision loss in patients with diabetic retinopathy.
鲁布昔多林（RBX）是一种抗血管内皮生长因子（抗VEGF）药物，用于治疗糖尿病性视网膜病变，主要通过玻璃体内注射给药。为了提供一种安全有效的RBX给药方法，本研究旨在开发使用第5代聚酰胺胺（PAMAM）树枝状大分子的RBX纳米颗粒来治疗糖尿病性视网膜病变。测定了RBX与PAMAM树枝状大分子拟合物的载药效率和体外释放情况，并选择了显示出最高可能载药效率的络合比。1:1、2.5:1和5:1络合物的载药效率（%）分别为89.2%、96.4%和97.6%。1:1、2.5:1和5:1络合物的载药量分别为1.6%、4.0%和7.2%。相比之下，5:1络合物在上述测量中显示出最佳结果。体外释放研究表明，在8小时内，1:1、2.5:1和5:1络合物中RBX的释放率分别为37.5%、35.9%和77.0%。特别是，5:1络合物显示出最高的药物释放率。此外，粒度测量表明，空PAMAM树枝状大分子的直径为214.9±8.5nm，而1:1、2.5:1、5:1络合物中负载PAMAM树枝状大分子的直径分别为461.0±6.4、482.4±12.5和420.0±7.1nm。多分散指数（PDI）表明，游离和负载的PAMAM树枝状大分子之间的PDI没有显著变化。ζ电位测量表明，由于存在阴离子和阳离子末端结构，游离和负载的纳米颗粒都具有中性电荷。此外，该制剂对MIO-M1细胞系的活力具有明显的安全性。这种纳米制剂将改善抗VEGF治疗的疗效和RBX的生物利用度，以预防糖尿病性视网膜病变患者的视力丧失。
