Imiquimod（IMQ）是一种免疫调节药物，已批准用于治疗浅表型基底细胞癌、日光性角化病、外生殖器疣和肛周疣。然而，IMQ乳膏（Aldara®）存在一些缺点，包括皮肤渗透性差、局部毒性大和患者顺从性因为是局部药物选项而受到损害。我们的研究旨在首次采用混合实验设计方法开发和优化含IMQ的纳米结构脂质体（NLCs）。然后将优化的配方作为替代剂量形式添加到基质型局部贴片中用于局部应用，并与商业产品的性能进行比较，评估其在不同皮层中的IMQ沉积。此外，我们的工作还尝试通过审查分析方法和实验设计并在可能的情况下减少能源和溶剂消耗来突出实施环境友好型实践在我们的IMQ-NLCs配方开发中的可能性。 本研究选择了十八醇、油酸、Tween® 80（聚山梨醇80）和Gelucire® 50/13（硬脂酸聚氧乙烯-32甘油酯）进行配方开发。使用2k因子设计和中心复合设计优化了配方。优化的配方的平均粒径、聚集度指数和ζ电位分别为75.6纳米、0.235和-30.9毫伏/秒。随后，开发了一种含IMQ-NLCs的基质型贴片，并显着提高了IMQ在更深层皮肤中的沉积。贴片中IMQ的沉积量在真皮层和受体室中分别为3.3 ± 0.9微克/平方厘米和12.3 ± 2.2微克/平方厘米，而商业乳膏仅沉积了1.0 ± 0.8微克/平方厘米和1.5 ± 0.5微克/平方厘米的IMQ。 总之，IMQ-NLC负载贴片代表了一种潜在的局部治疗皮肤癌的选择，可提高患者顺从性。©2023 Kim等人。

Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option.Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible.In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively.In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.© 2023 Kim et al.