Exploring the potential of combining menthol-thymol deep eutectic solvent and solid microneedles for cutaneous...

Area of Science:

• Dermal drug delivery
• Biomaterials science
• Pharmaceutical technology

Background:

• Transdermal peptide delivery faces challenges due to stratum corneum barrier properties (hydrophilicity, high molecular weight).
• Deep eutectic solvents (DESs) are emerging as chemical enhancers to improve skin permeation.
• Microneedles (MNs) offer a physical method to bypass the stratum corneum barrier.

Purpose of the Study:

• To evaluate the permeation enhancement of pentapeptide GVAPG using menthol-thymol DES (MT-DES).
• To assess the combined effect of MT-DES and microneedles (MNs) on GVAPG skin permeation.
• To investigate the stability of GVAPG in MT-DES compared to traditional buffers.

Main Methods:

• Ex vivo permeation studies of GVAPG in porcine skin using MT-DES and/or solid MNs.
• Stability testing of GVAPG in MT-DES versus phosphate-buffered saline (PBS) against skin enzymes.
• MALDI-MS imaging for GVAPG distribution and molecular dynamics simulations for interaction analysis.

Main Results:

• The combination of MT-DES and MNs significantly enhanced GVAPG permeation more than either enhancer alone.
• MT-DES improved GVAPG stability by reducing degradation from skin proteolytic enzymes.
• GVAPG showed an elongated conformation in MT-DES, suggesting easier liberation and permeation.

Conclusions:

• Combining MT-DES with MNs is a highly effective strategy for enhancing peptide skin permeation and stability.
• This synergistic approach holds potential for reducing application frequency in transdermal peptide therapies.
• Further research with diverse peptides is warranted to validate these findings.