Transdermal delivery of Acheta domesticus protein hydrolysate using nanostructured lipid carriers and Derma Stamp: Does the combination of lipid-based formulation and a physical technique add value for permeation and retention?

Acheta domesticus protein hydrolysate (PH) is a natural anti-skin aging compound, but its effectiveness is hindered by poor skin penetration due to its hydrophilicity and high molecular weight. This study aimed to compare the enhancement of PH skin delivery by increasing lipophilicity with nanostructured lipid carriers (NLCs) and bypassing the skin barrier using physical techniques, including Derma Stamp and dissolving microneedles (MNs). Fluorescein isothiocyanate (FITC)-tagged PH was prepared to track the transdermal transport, and complexed with dioctyl sodium sulfosuccinate (DSS) to be encapsulated into NLCs, prepared using a melt emulsification method. Skin delivery was evaluated in terms of skin permeation and skin retention using Franz diffusion cells. The FITC-PH loaded NLCs had a particle size of 238.9 ± 0.8 nm, a polydispersity index of 0.3 ± 0.0, a zeta potential of −23.6 ± 1.0 mV, and an encapsulation efficiency of 65.1 ± 2.1 %. The MNs, prepared with polyvinylpyrrolidone K30 and polyvinyl alcohol (38:15 wt ratio), had uniform sharp needles and a high FITC-PH loading capacity of 97.2 ± 1.9 %. PH permeation was most effectively enhanced through physical barrier bypassing, particularly with the Derma Stamp, followed by MNs and finally due to incorporation into NLCs. Notably, when utilizing the Derma Stamp, converting the aqueous solution of PH into an NLC formulation added positive benefits by significantly improving skin retention. In conclusion, it was suggested that while physical enhancement methods are crucial for permeation of the PH, optimizing formulation characteristics, such as incorporation into NLCs, further increased the overall effectiveness of skin delivery.