Scientific Reports ( IF 3.8 ) Pub Date : 2022-08-20 , DOI: 10.1038/s41598-022-18671-1 Humzah Jamshaid 1, 2 , Fakhar Ud Din 1 , Maimoona Malik 1 , Muhammad Mukhtiar 3 , Han Gon Choi 4 , Tofeeq Ur-Rehman 1 , Gul Majid Khan 1, 5
Herein, Imiquimod (IMQ) was incorporated in nanotransethosomes (nTES) to develop the IMQ-nTES nano-drug delivery system. IMQ-nTES was optimized using 23 factorial design. The optimized formulation was expressed with a particle size of 192.4 ± 1.60 nm, Poly-dispersibility of 0.115 ± 0.008, and IMQ percent entrapment efficiency of 91.05 ± 3.22%. Smooth and round morphology of IMQ-nTES vesicles was confirmed by TEM micrographs. Moreover, FTIR results have shown drug-excipient compatibility. The IMQ-nTES was laden inside the low molecular weight chitosan gel, which exhibited easy application, spreadability and no irritation to the applied skin. The release pattern has clearly exhibited improved dissolution properties of IMQ with the provision of the sustain release pattern. Higher IMQ content was deposited in deeper epidermis and dermis with IMQ-nTES gel, in contrast to ALDARA. In vivo, comparative toxicity study on BALB/c mice has shown significantly reduced (p < 0.001) psoriatic area severity index (PASI) score and less increment in ear thickness. Epidermal hyperplasia was an obvious finding with ALDARA which was, providentially, minimal in IMQ-nTES gel-treated skin. FTIR analysis of skin tissue has shown an enhancement of lipid and protein content in the ALDARA group, however, in the IMQ-nTES group no such change was observed. With ALDARA application, CD4+ T-cells and constitutive NF-κβ expression were significantly elevated, in comparison to the IMQ-nTES gel treated group. Moreover, the adequate expression of IFN-γ and cytotoxic CD8+ T-cells were suggesting the preserved IMQ efficacy with IMQ-nTES gel. Quantification of cutaneous as well as systemic inflammatory markers has also suggested the reduced psoriatic potential of IMQ-nTES gel. In essence, IMQ-nTES gel can be a suitable alternative to ALDARA owing to its better safety profile.
中文翻译:
咪喹莫特皮肤毒性的减少;咪喹莫特纳米转体凝胶与 5% 市售乳膏对 BALB/c 小鼠的皮肤毒性比较分析
在此,将咪喹莫特(IMQ)纳入纳米转酶体(nTES)中,开发了IMQ-nTES纳米药物递送系统。IMQ-nTES 使用 2 3因子设计进行优化。优化后的配方粒径为 192.4 ± 1.60 nm,多分散性为 0.115 ± 0.008,IMQ 百分比包封率为 91.05 ± 3.22%。通过 TEM 显微照片证实了 IMQ-nTES 囊泡的光滑和圆形形态。此外,FTIR 结果显示了药物与赋形剂的相容性。IMQ-nTES 负载在低分子量壳聚糖凝胶内,具有使用方便、铺展性好、对皮肤无刺激等优点。通过提供持续释放模式,释放模式清楚地表现出 IMQ 溶出特性的改善。与 ALDARA 相比,IMQ-nTES 凝胶将更高的 IMQ 含量沉积在更深的表皮和真皮中。在体内,对 BALB/c 小鼠的比较毒性研究表明,银屑病区域严重程度指数 (PASI) 评分显着降低 (p < 0.001),耳朵厚度增加较少。表皮增生是 ALDARA 的一个明显发现,幸运的是,在 IMQ-nTES 凝胶处理的皮肤中,表皮增生是最小的。皮肤组织的 FTIR 分析显示 ALDARA 组的脂质和蛋白质含量有所增加,但在 IMQ-nTES 组中没有观察到这种变化。与 IMQ-nTES 凝胶治疗组相比,应用 ALDARA 后,CD4 + T 细胞和组成型 NF-κβ 表达显着升高。此外,IFN-γ 和细胞毒性 CD8 + T 细胞的充分表达表明 IMQ-nTES 凝胶保留了 IMQ 功效。皮肤和全身炎症标志物的量化也表明 IMQ-nTES 凝胶可降低银屑病的可能性。从本质上讲,IMQ-nTES 凝胶由于其更好的安全性,可以成为 ALDARA 的合适替代品。