State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, College of Ocean and Earth Sciences, Xiamen University , Xiamen 361102, PR China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources , Xiamen 361102, PR China.
Mol Pharm. 2017 Sep 5;14(9):3188-3200. doi: 10.1021/acs.molpharmaceut.7b00468. Epub 2017 Aug 18.
We report the development of sponge Haliclona sp. spicules, referred to as SHS, and its topical application in skin delivery of hydrophilic biomacromolecules, a series of fluorescein isothiocyanate-dextrans (FDs). SHS are silicious oxeas which are sharp-edged and rod-shaped (∼120 μm in length and ∼7 μm in diameter). SHS can physically disrupt skin in a dose-dependent manner and retain within the skin over at least 72 h, which allows sustained skin penetration of hydrophilic biomacromolecules. The magnitude of enhancement of FD delivery into skin induced by SHS treatment was dependent on its molecular weight. Specifically, SHS topical application enhanced FD-10 (MW: 10 kDa) penetration into porcine skin in vitro by 33.09 ± 7.16-fold compared to control group (p < 0.01). SHS dramatically increased the accumulation of FD-10 into and across the dermis by 62.32 ± 13.48-fold compared to the control group (p < 0.01). In vivo experiments performed using BALB/c mice also confirmed the effectiveness of SHS topical application; the skin absorption of FD-10 with SHS topical application was 72.14 ± 48.75-fold (p < 0.05) and 15.39 ± 9.91-fold (p < 0.05) higher than those from the PBS and Dermaroller microneedling, respectively. Further, skin irritation study and transepidermal water loss (TEWL) measurement using guinea pig skin in vivo indicated that skin disruption induced by SHS treatment is self-limited and can be recovered with time and efficiently. SHS can offer a safe, effective, and sustained skin delivery of hydrophilic biomacromolecules and presents a promising platform technology for a wide range of cosmetic and medical applications.
我们报告了海绵 Haliclona sp. 骨针（简称 SHS）的开发及其在亲水性生物大分子的皮肤递送上的应用，其中包括一系列荧光素异硫氰酸酯-葡聚糖（FDs）。SHS 是一种硅质骨针，具有锋利的边缘和棒状（约 120 μm 长，7 μm 直径）。SHS 可以以剂量依赖的方式物理破坏皮肤，并在至少 72 小时内保留在皮肤内，从而允许亲水性生物大分子持续渗透皮肤。SHS 处理诱导的 FD 递送到皮肤中的增强程度取决于其分子量。具体而言，与对照组相比，SHS 局部应用将 FD-10（MW：10 kDa）渗透到猪皮中的倍数增加了 33.09 ± 7.16 倍（p < 0.01）。与对照组相比，SHS 显著增加了 FD-10 在内皮和真皮中的积累量，分别增加了 62.32 ± 13.48 倍（p < 0.01）。使用 BALB/c 小鼠进行的体内实验也证实了 SHS 局部应用的有效性；与 PBS 和 Dermaroller 微针相比，SHS 局部应用后 FD-10 的皮肤吸收率分别提高了 72.14 ± 48.75 倍（p < 0.05）和 15.39 ± 9.91 倍（p < 0.05）。此外，体内豚鼠皮肤的皮肤刺激研究和经皮水分流失（TEWL）测量表明，SHS 处理引起的皮肤破坏是自限性的，可以随时间和效率恢复。SHS 可为亲水性生物大分子提供安全、有效和持续的皮肤传递，并为广泛的美容和医疗应用提供有前途的平台技术。
