{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T21:45:54Z","timestamp":1740174354833,"version":"3.37.3"},"reference-count":0,"publisher":"Maad Rayan Publishing Company","content-domain":{"domain":["bi.tbzmed.ac.ir"],"crossmark-restriction":false},"short-container-title":["Bioimpacts"],"abstract":"<jats:p>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 to skin permeation. Methods: In an attempt to concurrently solve these limitations, here we have studied different short-mid chain fatty acids (C6-C18) conjugates of dipeptide KT. Different fatty acid chain lengths of C6, C8, C10, C12, C14, C16, and C18 were considered to be conjugated with KT and screened in-silico. Of those, C8, C10, and C12 were preferred and synthesized alongside two controls of the parent drug (KT) and C16 (Pal-KT) as the commercialized form to be studied mechanistically. Subsequently, they were structurally characterized and underwent preformulation, supramolecular investigations (e.g., thermal behavior, solubility, surface-acting, crystalline structure), and skin absorption studies. Results: Data showed that the synthesized conjugates substantially outperformed Pal-KT in terms of molecular weight, lipophilicity, melting point, and aqueous solubility. In addition, unlike KT, they all demonstrated amphiphilicity-related features. The maximum and minimum skin permeation were assigned to C8-KT (33.2%) and KT (0.004%). Moreover, permeability coefficients (Kp) of the C8-KT, C10-KT, C12-KT, and C16-KT were calculated to be about 22000, 3800, 3400, and 1600 times higher than KT, respectively. Conclusion: Conjugating lower molecular weight fatty acids and optimizing lipophilicity can enhance molecular properties, skin absorption, and the ability to form supramolecular structures. This, in turn, leads to the development of superior anti-wrinkle products and formulations.<\/jats:p>","DOI":"10.34172\/bi.2023.27558","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T06:17:58Z","timestamp":1692166678000},"update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimized cutaneous delivery of anti-wrinkle dipeptide KT via molecular modification: Preformulation, permeation, and the importance of conjugate chain length"],"prefix":"10.34172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0632-5397","authenticated-orcid":true,"given":"Mahsa","family":"Sayed Tabatabaei","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, \u200eShahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farzad","family":"Kobarfard","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of \u200eMedical Sciences, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Aboofazeli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, \u200eShahid Beheshti University of Medical Sciences, Tehran, Iran"},{"name":"Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, \u200eIran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorour","family":"Ramezanpour","sequence":"additional","affiliation":[{"name":"Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-7113","authenticated-orcid":true,"given":"Hamid Reza","family":"Moghimi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, \u200eShahid Beheshti University of Medical Sciences, Tehran, Iran"},{"name":"Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, \u200eIran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"20123","published-online":{"date-parts":[[2023,7,18]]},"container-title":["BioImpacts"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bi.tbzmed.ac.ir\/Inpress\/bi-27558.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bi.tbzmed.ac.ir\/Inpress\/bi-27558.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T12:22:34Z","timestamp":1719231754000},"score":1,"resource":{"primary":{"URL":"https:\/\/bi.tbzmed.ac.ir\/Inpress\/bi-27558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,18]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34172\/bi.2023.27558","relation":{},"ISSN":["2228-5652","2228-5660"],"issn-type":[{"type":"print","value":"2228-5652"},{"type":"electronic","value":"2228-5660"}],"subject":[],"published":{"date-parts":[[2023,7,18]]},"assertion":[{"value":"Tabriz University of Medical Sciences","name":"journal_owner","label":"Journal Owner"},{"value":"Tabriz University of Medical Sciences","name":"journal_publisher","label":"Journal Publisher"},{"value":"2022-08-10","order":1,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}