Donthi Mahipal Reddy, Saha Ranendra Narayan, Singhvi Gautam, Dubey Sunil Kumar
Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Pilani Campus, Pilani 333031, Rajasthan, India.
Pharmaceutics. 2023 Feb 22;15(3):736. doi: 10.3390/pharmaceutics15030736.
The current study aimed to develop a topical emulgel of dasatinib (DTB) for rheumatoid arthritis (RA) treatment to reduce systemic side effects. The quality by design (QbD) approach was employed to optimize DTB-loaded nano-emulgel using a central composite design (CCD). Emulgel was prepared using the hot emulsification method, and then the particle size (PS) was reduced using the homogenization technique. The PS and % entrapment efficiency (% EE) were found to be 172.53 ± 3.33 nm (0.160 ± 0.014 PDI) and 95.11 ± 0.16%, respectively. The nano-emulsion (CF018 emulsion) in vitro drug release profile showed sustained release (SR) up to 24 h. MTT assay results from an in vitro cell line study revealed that formulation excipients had no effect, whereas emulgel showed a high degree of internalization. Furthermore, emulgel treatment significantly reduced LPS-induced TNF-α production in RAW 264.7 cells. The spherical shape was depicted in FESEM images of optimized nano-emulgel (CF018 emulgel) formulation. Ex vivo skin permeation was significantly increased when compared to the free drug-loaded gel (FDG). In vivo data revealed that the optimized CF018 emulgel is a non-irritant and is safe. In terms of paw swelling, the FCA-induced arthritis model demonstrated that the CF018 emulgel reduced paw swelling percentage compared to adjuvant-induced arthritis (AIA) control group. Following clinical testing in the near future, the designed preparation could be a viable alternative treatment for RA.
本研究旨在开发一种用于治疗类风湿性关节炎（RA）的达沙替尼（DTB）外用乳凝胶，以减少全身副作用。采用质量源于设计（QbD）方法，使用中心复合设计（CCD）优化载有DTB的纳米乳凝胶。采用热乳化法制备乳凝胶，然后使用均质技术减小粒径（PS）。发现PS和包封率（%EE）分别为172.53±3.33nm（0.160±0.014PDI）和95.11±0.16%。纳米乳液（CF018乳液）的体外药物释放曲线显示长达24小时的缓释（SR）。体外细胞系研究的MTT分析结果表明制剂辅料无影响，而乳凝胶显示出高度的内化作用。此外，乳凝胶处理显著降低了RAW 264.7细胞中脂多糖诱导的TNF-α产生。优化后的纳米乳凝胶（CF018乳凝胶）制剂的场发射扫描电子显微镜（FESEM）图像显示为球形。与载有游离药物的凝胶（FDG）相比，离体皮肤渗透显著增加。体内数据显示，优化后的CF018乳凝胶无刺激性且安全。在爪肿胀方面，弗氏完全佐剂（FCA）诱导的关节炎模型表明，与佐剂诱导的关节炎（AIA）对照组相比，CF018乳凝胶降低了爪肿胀百分比。在不久的将来进行临床测试后，所设计的制剂可能成为RA的一种可行替代治疗方法。
