Optimized Cutaneous Delivery of Anti-wrinkle Dipeptide KT via Molecular Modification: Preformulation, Permeation, and the Importance of Conjugate Chain Length

Introduction: Anti-aging peptides, such as dipeptide KT, are promising rejuvenating agents and have recently received significant attention. However, their hydrophilic nature makes skin absorption therapeutically inadequate. The excessive hydrophilicity of peptides is partially solved by lipoidal conjugates, however, the increased molecular weight due to conjugation creates a new obstacle permeation. Methods: In an attempt concurrently solve these limitations, here we studied different short-mid chain fatty acids (C6-C18) conjugates KT. Different acid lengths C6, C8, C10, C12, C14, C16, C18 were considered be conjugated with KT screened in-silico. Of those, C12 preferred synthesized alongside two controls parent drug (KT) C16 (Pal-KT) commercialized form mechanistically. Subsequently, they structurally characterized underwent preformulation, supramolecular investigations (e.g., thermal behavior, solubility, surface-acting, crystalline structure), studies. Results: Data showed that substantially outperformed Pal-KT in terms weight, lipophilicity, melting point, aqueous solubility. addition, unlike all demonstrated amphiphilicity-related features. maximum minimum permeation assigned C8-KT (33.2%) (0.004%). Moreover, permeability coefficients (Kp) C8-KT, C10-KT, C12-KT, C16-KT calculated about 22000, 3800, 3400, 1600 times higher than respectively. Conclusion: Conjugate selection lower optimal lipophilicity can positively affect properties, absorption, ability structures consequently pave way ‘better’ anti-wrinkle products formulations.