Liang XueJiao, Zhang JiaLiang, Ou HuiLong, Chen Jun, Mitragotri Samir, Chen Ming
State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, Department of Marine Biological Science & Technology, College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China.
Department of Pharmacy, Dong Fang Hospital (Fuzhou General Hospital), Medical College of Xiamen University, Xiamen University, Fouzhou 350025, China.
Mol Ther Nucleic Acids. 2020 Jun 5;20:639-648. doi: 10.1016/j.omtn.2020.04.003. Epub 2020 Apr 18.
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.
我们报道了海绵Haliclona sp.骨针（SHS）与阳离子柔性脂质体（CFL）联合进行局部给药，以提高小干扰RNA（siRNA）在体外和体内进入活皮肤细胞的递送效率。SHS可作为新型微针进行局部应用，通过在角质层中形成大量新的微通道来克服皮肤屏障。随后，精心设计的CFL也可作为纳米载体进行局部应用，通过这些微通道将siRNA递送至皮肤深层，从而克服皮肤细胞膜屏障，促进其细胞内化。SHS与CFL（脂质含量0.05%，w/v）联合局部应用，即CFL(0.05%)，与对照组相比，在体外可使siRNA的皮肤渗透率提高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与CFL(0.05%)，在体内所有给药区域均导致甘油醛-3-磷酸脱氢酶（GAPDH）敲低29.21%±1.41%，这与皮下注射部位的GAPDH蛋白敲低率无显著差异。然而，高敲低率仅出现在注射部位附近（<0.5 cm）。总之，本研究通过联合使用SHS和精心设计的CFL，提供了一种有前景的siRNA局部递送策略。
