We report the topical administration of sponge Haliclona sp. Spicules (SHS) combined with cationic flexible liposomes (CFL) to increase the delivery of small interfering RNA (siRNA) into viable skin cells in vitro and in vivo. SHS can be applied topically as novel microneedles to overcome skin barrier by creating plenty of new microchannels in stratum corneum. Subsequently, well-designed CFL can be also utilized topically as nanocarriers to overcome skin cells membrane by delivering siRNA to skin deep layers through these microchannels and thereby facilitating their cell internalization. The topical application of SHS in combination with CFL (0.05% of lipids, w/v), referred to as CFL(0.05%), enhanced siRNA skin penetration in vitro by 72.95 ± 2.97-fold compared to control group (p < 0.001). Further, the topical application of SHS in combination with CFL(0.05%) on female BALB/c mice skin resulted in 29.21% ± 1.41% of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) knockdown at all application area in vivo, which was not significantly different from the GAPDH protein knockdown rate in the subcutaneous injection center. However, the high knockdown rate only appears in the vicinity (<0.5 cm) of the injection center. In sum, this study provides a promising strategy of topical delivery of siRNA by the combined used of SHS and well-designed CFL.

我们报告了海绵Haliclona sp。的局部给药。针状体（SHS）与阳离子脂质体的柔性（CFL）组合以增加成可行的皮肤细胞递送的小干扰RNA（siRNA）在体外和体内。SHS可以作为新型微针局部应用，通过在角质层中创建大量新的微通道来克服皮肤屏障。随后，经过精心设计的CFL还可通过将siRNA通过这些微通道输送到皮肤深层，从而促进其细胞内在化，从而在局部用作纳米载体以克服皮肤细胞膜。SHS与CFL（0.05％的脂质，w / v）结合的局部应用被称为CFL（0.05％），可增强siRNA在体外的皮肤渗透与对照组相比，降低了72.95±2.97倍（p <0.001）。此外，在雌性BALB / c小鼠皮肤上局部应用SHS和CFL（0.05％）的组合在体内所有应用区域均导致29.21％±1.41％的甘油三磷酸脱氢酶（GAPDH）降低，这并非如此。与皮下注射中心的GAPDH蛋白敲除率有显着差异。但是，较高的击倒率仅出现在注射中心附近（<0.5 cm）。总而言之，这项研究通过结合使用SHS和精心设计的CFL，提供了一种有希望的局部递送siRNA的策略。