Enhanced Skin Delivery of Therapeutic Peptides Using Spicule-Based Topical Delivery Systems

• Published in: Pharmaceutics 2021-12, Vol.13 (12), p.2119
• Main Authors: Zhang, Chi, Duan, Jiwen, Huang, Yongxiang, Chen, Ming
• Format: Article
• Language: English
• Subjects: cyclosporine A; dermal delivery; Diabetes; Insulin; Laboratory animals; Microscopy; Morphology; Nanoparticles; Peptides; Rodents; spicules; therapeutic peptides; transdermal delivery
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13122119

This study reports two therapeutic peptides, insulin (INS, as a hydrophilic model peptide) and cyclosporine A (CysA, as a hydrophobic one), that can be administrated through a transdermal or dermal route by using spicule-based topical delivery systems in vitro and in vivo. We obtained a series of spicules with different shapes and sizes from five kinds of marine sponges and found a good correlation between the skin permeability enhancement induced by these spicules and their aspect ratio . In the case of INS, Sponge sp. spicules (SHS) dramatically increased the transdermal flux of INS (457.0 ± 32.3 ng/cm /h) compared to its passive penetration (5.0 ± 2.2 ng/cm /h) in vitro. Further, SHS treatment slowly and gradually reduced blood glucose to 13.1 ± 6.3% of the initial level in 8 h, while subcutaneous injection resulted in a rapid blood glucose reduction to 15.9 ± 1.4% of the initial level in 4 h, followed by a rise back to 75.1 ± 24.0% of the initial level in 8 h. In the case of CysA, SHS in combination with ethosomes (SpEt) significantly ( < 0.05) increased the accumulation of CysA in viable epidermis compared to other groups. Further, SpEt reduced the epidermis thickness by 41.5 ± 9.4% in 7 days, which was significantly more effective than all other groups. Spicule-based topical delivery systems offer promising strategies for delivering therapeutic peptides via a transdermal or dermal route.