Anuradha Urati, Bhavana Valamla, Chary Padakanti Sandeep, Kalia Nitin Pal, Mehra Neelesh Kumar
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India.
Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Ministry of Chemicals and Fertilizers, Government of India, Hyderabad 500037, Telangana, India.
Pathophysiology. 2024 Nov 25;31(4):680-698. doi: 10.3390/pathophysiology31040049.
To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol 934 to obtain the DLMGO-G. Nanoemulsion was characterized for particle size, and polydispersity index (PDI) was obtained by Malvern Zetasizer (Zetasizer Nano ZS, Malvern, AL, USA), and morphology by TEM (JEM 1400, JOEL, Akishima, Japan). Furthermore, in vitro cell line and in vivo studies were carried out. The developed nanoemulsion showed a globule size of 28.04 ± 0.23 nm and PDI of 0.07 ± 0.01. The morphology of nanoformulations by TEM confirmed the spherical and uniform nature. Further, the nanoformulation in in vitro cell line experiments revealed that the IC50 value was increased by 1.52 times compared to the drug solution. The treatment groups have shown that fibroblast morphologies were spindle-shaped, suggesting that nanoformulation was compatible with the cells and developed normally on nanoformulation. It also reduced ROS with improved internalization more than the control group. The in vitro wound healing model also revealed that nanoformulation had better wound healing activity. In the in vivo diabetic wound studies on male SD rats, the levels of inflammatory markers such as TNF-α, IL-6, IL-22, and IL-1β declined significantly when treated with DLMGO-G. IL-10 levels significantly increased compared to the diseased group, and MMP-9 levels were remarkably decreased compared to the diseased group. Furthermore, histopathological studies showed the regeneration and granulation of tissues. Thus, these findings indicate that FA-loaded nanoemulgel greatly accelerates the healing of wounds in diabetic rats.
为研究新型局部用制剂[阿魏酸负载纳米乳凝胶(DLMGO-G)]的抗炎、抗氧化及糖尿病伤口愈合特性。对用柠檬草油研制的阿魏酸纳米乳在糖尿病伤口愈合方面进行了研究。进一步将纳米乳加入1%的卡波姆934中以获得DLMGO-G。通过马尔文粒度分析仪(美国马尔文公司的Zetasizer Nano ZS)测定纳米乳的粒径及多分散指数(PDI),通过透射电子显微镜(日本电子株式会社的JEM 1400)观察其形态。此外,还进行了体外细胞系和体内研究。所研制的纳米乳的球粒大小为28.04±0.23 nm,PDI为0.07±0.01。透射电子显微镜观察纳米制剂的形态证实其呈球形且均匀。此外,体外细胞系实验显示,纳米制剂的半数抑制浓度(IC50)值相比药物溶液增加了1.52倍。治疗组显示成纤维细胞形态呈纺锤形,表明纳米制剂与细胞相容且在纳米制剂上正常生长。与对照组相比,其还减少了活性氧(ROS)并提高了内化作用。体外伤口愈合模型也显示纳米制剂具有更好的伤口愈合活性。在雄性SD大鼠的体内糖尿病伤口研究中,用DLMGO-G治疗时,肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-22(IL-22)和白细胞介素-1β等炎症标志物水平显著下降。与患病组相比,白细胞介素-10水平显著升高,基质金属蛋白酶-9(MMP-9)水平显著降低。此外,组织病理学研究显示组织再生和肉芽形成。因此,这些研究结果表明,负载阿魏酸的纳米乳凝胶能极大地加速糖尿病大鼠伤口的愈合。