Spirocyclic Acetal-Modified Dextran as a pH-Sensitive Solubility Switching Material



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The development of tools used to control the administration and localization of therapeutic agents has enabled advancement of healthcare and disease therapeutics. Drug delivery systems use biocompatible tools to control timing, location and conditions for releasing therapeutic agents throughout the body. A previously synthesized biopolymer – acetalated dextran (Ac-Dex) – is a biopolymer known for its solubility switching properties as it is modified using acetal groups on a watersoluble dextran polymer to make the molecule insoluble in aqueous material. Upon acid hydrolysis the modification groups detach from the molecule causing it to revert to its preliminary soluble state. Ac-Dex has shown good qualities for a drug delivery polymer but is limited by the high hydroxyl coverage which upon degradation releases potentially undesirable quantities of byproducts, in addition to the faster degrading variations of the polymer that have limited solubility and shelf life. To address these limitations of Ac-Dex, the acetal modifying group can be analyzed to understand its effect on the function of the biodegradable polymer. Spirocyclic acetal modified dextran (SpAc – Dex) is a new polymer for drug delivery purposes that models previously synthesized acetal-dextran pathways, but with variations on the acetal modification group. Three enol ethers with a 5-, 6- and 7-member ring were attached to a dextran polymer and samples were collected at timepoints over 24 h to form a library of nine testable materials. Each sample has a variation on its degree of modification of either an acyclic acetal attachment with only one bond to dextran, or cyclic acetal attachment, with two bonds to dextran. Each polymer was comprehensively characterized using NMR to find cyclic vs acyclic acetal modification ratio and understand the properties of each polymer. The degradation rate, and cell viability of each material was tested to determine SpAc-Dex’s quality as a biomaterial. The 5-member and 6-member ring acetal modifications proved to be able to switch solubility with few modifications and degrade under acidic conditions, while the 7-membered ring showed little degradation under biologically acidic conditions and high cyclic modifications.



Chemistry, Polymers, Drug Delivery, Spectroscopy