Skin Delivery of Hydrophilic Biomacromolecules Using Marine Sponge Spicules

Abstract

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.

<p>Topical Application of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Combination with Sponge Spicules for Treatment of Photoaging</p>

“…In the meanwhile, their combined use induced some inflammatory infiltrate immediately, and the latter completely disappeared 24 h later ( Figure 7A and B). Compared to the single use of SHSs, 12 the combination of hucMSC-Exos and SHSs showed a faster recovery of the skin from the resulting inflammatory infiltration. This might be associated with the immunomodulatory function of MSC-Exos.…”

“…29,30 Recently, we reported that SHSs could be used as a novel microneedle system to promote the skin absorption of hydrophilic macromolecules. 12 SHSs can readily pierce the skin through gentle massage, and 10 mg of them may create more than 1000 microchannels (with a depth of 42.2 ± 14.9 μm) per mm 2.12 SHSs (or the microchannels caused) will gradually disappear from the skin within three days due to normal desquamation. Very importantly, SHSs may be suited to any desired skin location and area.…”

“…spicules (SHSs) as a novel kind of microneedles for enhancing skin delivery of hydrophilic biomacromolecules. 12 SHSs are silicious oxeas, which can penetrate the skin by simple massage and create over 1000 microchannels per mm 2 in the skin. 12 Also, it has been shown that the combination of SHSs and flexible liposomes may produce a synergic effect to dramatically improve the skin delivery of hyaluronic acid (~250 kDa).…”

“…12 SHSs are silicious oxeas, which can penetrate the skin by simple massage and create over 1000 microchannels per mm 2 in the skin. 12 Also, it has been shown that the combination of SHSs and flexible liposomes may produce a synergic effect to dramatically improve the skin delivery of hyaluronic acid (~250 kDa). 13 Thus, we speculated that SHSs could facilitate the skin delivery of MSC-Exos and subsequently achieve the desired therapeutic results.…”

Development of Sponge Microspicule Cream as a Transdermal Delivery System for Protein and Growth Factors from Deer Antler Velvet Extract

“…Monactines are needle-like structures of sponge spicules with the tip growing out from two opposite sites known as "spicules." 14,15) The use of Spongillia as a dermabrasive has been reported to be a natural alternative approach for treating skin problems, including hyperpigmentation of different etiology, fine wrinkles, sun-damaged skin, superficial scars, comedones, enlarged facial pores, and dull skin. Upon massaging Spongillia spicules onto the skin, they can mechanically separate the epidermal layers and reduce keratinocyte cohesion but increase stratum corneum sloughing and remove loosen keratinocyte.…”