Synthesis of α,ω-bis-Mercaptoacyl Polys and Development of Thioether Cross-Linked Liposome Scaffolds for Sustained Release of Drugs

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-03, Vol.29 (6)
• Main Authors: Mourtas, Spyridon, Kourmoulakis, Georgios, Kremezis, Stavros, Klepetsanis, Pavlos, Antimisiaris, Sophia G
• Format: Article
• Language: English
• Subjects: Ethylene glycol; Ethylene oxide; Evaluation
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29061312

With the aim to develop novel scaffolds for the sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt)-protected mercapto acids, followed by the removal of the acid labile S-Mmt group. This method allowed for the efficient synthesis of the title compounds in high yield and purity, which were further used in the development of a thioether cross-linked liposome scaffold, by thia–Michael reaction of the terminal thiol groups with pre-formed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by [sup.1]H-NMR, using a Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion NMR experiment ([sup.1]H-NMR CPMG), which allowed for real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nano-sized characteristics of the initial liposomes and allowed for the sustained release of calcein (which was used as a hydrophilic dye and a hydrophilic drug model), providing evidence for the efficient synthesis of a novel drug release scaffold consisting of nanoliposome building blocks.