This study aimed to formulate nano-cubosomes (NCs) co-loaded with capsaicin (CAP) and thiocolchicoside (TCS) to enhance their bioavailability and minimize associated potential side effects through transdermal delivery alongside their synergistic activity. Twenty seven (27) nano-cubosomal dispersions were prepared according to Box-Behnken factorial design and the effect of CAP, TCS, glyceryl mono oleate (GMO) and poloxamer 407 (P407) concentrations on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were assessed. The results revealed that the optimized formulation exhibited a mean droplet size of 503 ± 10.3 nm, PDI of 0.405 ± 0.02, zeta potential of −10.0 ± 1.70 mV and entrapment efficiency of 86.9 ± 3.56 %. The anti-inflammatory effect of optimized formulation was studied in rats by injecting carrageenan to induce edema. The results of study showed that transdermal application of nano-cubosomes co-loaded with CAP and TCS significantly (p value < 0.05) improved carrageenan induced inflammation compared with standard treatment. The analgesic activity of optimized formulation was evaluated in rats by using Eddy’s hot plate method. The findings of analgesic activity illustrated that the analgesic effects exhibited by test formulation may be associated with increased licking period and inhibition of prostaglandins level. In conclusion, the transdermal application of NCs co-loaded with CAP and TCS may be a promising delivery system for enhancing their bioavailability as well as synergistic analgesic and anti-inflammatory activity in gout management.

中文翻译：

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一种纳米复合材料能够在痛风治疗中同时克服辣椒素和硫代秋水仙苷的溶解度和渗透问题：纳米立方体的制造

本研究旨在配制共同负载辣椒素（CAP）和硫代秋水仙苷（TCS）的纳米立方体（NC），以增强其生物利用度，并通过透皮递送及其协同活性最大限度地减少相关的潜在副作用。根据 Box-Behnken 因子设计以及 CAP、TCS、单油酸甘油酯 (GMO) 和泊洛沙姆 407 (P407) 浓度对粒径、多分散指数 (PDI)、zeta 的影响，制备二十七 (27) 个纳米立方体分散体评估了潜力和包封效率。结果表明，优化后的配方平均液滴尺寸为503±10.3 nm，PDI为0.405±0.02，zeta电位为-10.0±1.70 mV，包封率为86.9±3.56%。通过注射角叉菜胶诱导水肿，研究优化配方的抗炎作用。研究结果表明，与标准治疗相比，透皮应用同时负载 CAP 和 TCS 的纳米立方体可显着（p 值 < 0.05）改善角叉菜胶引起的炎症。采用涡热板法评价优化制剂的大鼠镇痛活性。镇痛活性的结果表明，测试制剂所表现出的镇痛效果可能与增加舔舐时间和抑制前列腺素水平有关。总之，NCs 与 CAP 和 TCS 共同负载的透皮应用可能是一种有前景的递送系统，可提高其生物利用度以及在痛风治疗中的协同镇痛和抗炎活性。