Optimized 5-Fluorouridine Prodrug for Co-Loading with Doxorubicin in Clinically Relevant Liposomes.

ABSTRACT: Liposome-based drug delivery systems have allowed for better drug tolerability and longer circulation times but are often optimized for a single agent due to the inherent difficulty of co-encapsulating two drugs with differing chemical profiles. Here, we design and test a prodrug based on a ribosylated nucleoside form of 5-fluorouracil, 5-fluorouridine (5FUR), with the final purpose of co-encapsulation with doxorubicin (DOX) in liposomes. To improve the loading of 5FUR, we developed two 5FUR prodrugs that involved the conjugation of either one or three moieties of tryptophan (W) known respectively as, 5FUR-W and 5FUR-W3. 5FUR-W demonstrated greater chemical stability than 5FUR-W3 and allowed for improved loading with fewer possible byproducts from tryptophan hydrolysis. Varied drug ratios

SUBMITTER: Wu D 

PROVIDER: S-EPMC7830726 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature