Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, Minia, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.
Int J Nanomedicine. 2021 Jan 8;16:133-145. doi: 10.2147/IJN.S289828. eCollection 2021.
Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes.
The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses.
To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-α, NF-кB and COX-2 were assessed in paw tissue before and after treatment.
The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 ± 3.6 nm, and 83.6 ± 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 ± 0.25 µg/cm/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 ± 0.12 µg/cm/hr and 0.64 ± 0.09 µg/cm/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-α, NF-кB and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel.
The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.
类风湿关节炎（RA）是一种自身免疫性疾病，其基础是滑膜的慢性炎症。非甾体抗炎药（NSAIDs）常用于治疗 RA。然而，长期使用 NSAIDs 治疗方案会产生一系列不良事件，这会对患者的依从性和治疗效果产生负面影响。
本工作旨在实现载塞来昔布的 Spanlastic 纳米囊泡递药系统的靶向递送至炎症关节，避免全身给予大剂量药物。
为了开发用于塞来昔布经皮传递的 Spanlastic 纳米囊泡，采用改良的注射法，使用 Tween 80 或 Brij 作为边缘活性剂。对包封效率、囊泡大小、体外渗透和制备的纳米囊泡的形态进行了表征。用选定的配方制备了含 Carbopol 的凝胶，并对其澄清度、pH 值、流变性能和体外渗透进行了表征。开发了载有尼莫司汀的尼莫司汀和含尼莫司汀的凝胶进行比较。在弗氏完全佐剂诱导的关节炎大鼠模型中评价了选定配方的体内疗效。在治疗前后评估了爪组织中的不同炎症标志物，包括 TNF-α、NF-κB 和 COX-2。
所选 Spanlastic 纳米囊泡制剂的粒径和包封效率分别为 112.5±3.6nm 和 83.6±2.3%。与其他研究的制剂相比，该制剂显示出最高的经皮通量和渗透系数。载塞来昔布的 Spanlastics 凝胶显示出 6.9±0.25μg/cm/hr 的经皮通量，而载塞来昔布尼莫司汀的凝胶和未经处理的载塞来昔布凝胶分别显示出 5.2±0.12μg/cm/hr 和 0.64±0.09μg/cm/hr 的经皮通量。在 RA 动物模型中，与尼莫司汀载药凝胶、市售双氯芬酸钠凝胶和未经处理的载塞来昔布凝胶相比，载塞来昔布的 Spanlastics 凝胶显著降低了肿胀周长，并显著抑制了 TNF-α、NF-κB 和 COX-2 水平。
与商业和其他常规替代物相比，载 Spanlastic 纳米囊泡的凝胶代表了一种更有效的靶向治疗慢性炎症的局部治疗方法，如 RA。
