# Synthesis of α,ω-bis-Mercaptoacyl Poly(alkyl oxide)s and Development of Thioether Cross-Linked Liposome Scaffolds for Sustained Release of Drugs

## TL;DR

Researchers created a new type of liposome scaffold for slowly releasing drugs, using a novel synthesis method and real-time monitoring.

## Contribution

A new synthesis method for α,ω-bis-mercaptoacyl poly(alkyl oxide)s and a thioether cross-linked liposome scaffold for sustained drug release.

## Key findings

- The synthesis method produced high-yield and high-purity α,ω-bis-mercaptoacyl poly(alkyl oxide)s.
- The thioether cross-linked liposome scaffold preserved nano-sized characteristics and enabled sustained release of calcein.
- 1H-NMR CPMG experiments allowed real-time monitoring and optimization of the reaction process.

## Abstract

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 1H-NMR, using a Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion NMR experiment (1H-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.