Faculty of Pharmacy, Kindai University.
Faculty of Pharmacy, Keio University.
J Oleo Sci. 2024;73(12):1479-1491. doi: 10.5650/jos.ess24160.
Severe oral mucositis is a major cause of a low quality of life in patients; however, the therapeutic effect of traditional treatments is insufficient. Therefore, we designed a carbopol gel based on rebamipide nanocrystals (REB NCs) and gum arabic (GA-REB@NP), and investigated its efficacy in accelerating wound healing in a hamster model of oral mucositis. REB NCs were prepared by bead milling, and GA- REB@NP were prepared by incorporating REB NCs into a carbopol gel. The REB sizes were measured using a SALD-7100 and NanoSight LM10, and both powder X-ray diffraction and differential thermal analysis were used to analyze the crystalline form. Drug release from the gel formulations and therapeutic effects were evaluated using hamsters. The particles of milled-REB without GA were microsized, whereas the particle size of milled-REB with GA was in the range of 30-180 nm, and the crystalline form was similar to that of REB with or without bead milling. Next, we evaluated the characteristics of GA-REB@NP. The particle size of REB in GA-REB@NP was in the range of 45-200 nm, and drug release from GA-REB@NP was higher than that from the gel incorporating REB microcrystals (GA-REB@MP). In addition, REB nanoparticles were released from GA-REB@NP. Moreover, inhibitors of both clathrin- (dynasore) and caveolae-dependent endocytosis (nystatin) attenuated the enhanced REB levels in the cheek pouches of hamsters treated with GA-REB@NP. GA-REB@NP also enhanced the healing of the wound area compared with GA-REB@MP in hamsters injected with acetic acid. We prepared GA-REB@NP, which provided high REB delivery into the cheek pouch tissue via endocytosis. Additionally, we demonstrated that wound healing in acetic acid-injected hamsters was promoted by the application of GA-REB@NP.
严重的口腔黏膜炎是导致患者生活质量下降的主要原因；然而，传统治疗方法的疗效不足。因此，我们设计了一种基于瑞巴派特纳米晶体（REB NCs）和阿拉伯胶（GA-REB@NP）的卡波姆凝胶，并在口腔黏膜炎的仓鼠模型中研究了其加速伤口愈合的功效。通过珠磨法制备 REB NCs，通过将 REB NCs 掺入卡波姆凝胶中制备 GA-REB@NP。使用 SALD-7100 和 NanoSight LM10 测量 REB 粒径，使用粉末 X 射线衍射和差示热分析分析晶体形态。通过仓鼠评估凝胶制剂的药物释放和治疗效果。未经 GA 处理的研磨 REB 颗粒为微颗粒，而经 GA 处理的研磨 REB 颗粒粒径在 30-180nm 范围内，晶体形态与研磨或未经研磨的 REB 相似。接下来，我们评估了 GA-REB@NP 的特性。GA-REB@NP 中 REB 的粒径在 45-200nm 范围内，GA-REB@NP 的药物释放率高于包含 REB 微晶体的凝胶（GA-REB@MP）。此外，GA-REB@NP 中释放出 REB 纳米颗粒。此外，网格蛋白（dynasore）和小窝依赖内吞作用（制霉菌素）的抑制剂均减弱了 GA-REB@NP 处理的颊囊组织中增强的 REB 水平。与 GA-REB@MP 相比，GA-REB@NP 还促进了醋酸注射的仓鼠的伤口愈合。我们制备了 GA-REB@NP，通过内吞作用将高浓度的 REB 递送到颊囊组织中。此外，我们证明了 GA-REB@NP 的应用促进了醋酸注射的仓鼠的伤口愈合。
