Skin delivery of hyaluronic acid by the combined use of sponge spicules and flexible liposomes.

We demonstrated that the topical combined use of sponge Haliclona sp. spicules (SHS) and flexible liposomes (FL), referred to as SFLS (SHS-Flexible Liposomes combined System), can result in synergy to improve the skin absorption and deposition of hyaluronic acid (HA), especially in deep skin layers, both in vitro and in vivo. SHS treatment can result in skin micro-channels which are continuous, deep enough (48.6 ± 13.5 μm) and available in large quantities (850 ± 125 micro-channels per mm2). These micro-channels gradually closed up in 120 h and also allowed the intact vesicles of flexible liposomes and vesicle-bound or vesicle-encapsulated HA to penetrate into the skin-deep layers under the driving force of transdermal osmotic gradients. Specifically, SFLS topical application enhanced the penetration of FITC-HA (MW: 250 kDa) into porcine skin in vitro up to 23.2 ± 3.7%, which is 19.4 ± 3.1-fold (p < 0.001) that of a Phosphate Buffered Saline (PBS) group, 3.4 ± 0.5-fold (p < 0.01) that of an SHS group and 3.6 ± 0.6-fold (p < 0.01) that from the combined use of a Dermaroller and flexible liposomes. Moreover, SFLS can lead to significantly enhanced skin deposition of HA in all skin layers, especially in deep skin layers: up to 86.8 ± 4.1% of HA absorbed by skin was accumulated in deep skin layers. The effectiveness of SFLS topical application was also confirmed in vivo by using BALB/c mice. In addition, a skin irritation and toxicity study showed that the SFLS treatment may cause very minimal redness and the skin can recover in a short time. In sum, the combined use of SHS and FL (SFLS) offers a promising strategy to safely and effectively improve the skin delivery of hydrophilic biomacromolecules such as HA.