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Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes for Controlled, Localized Synthesis of Therapeutics
Author(s) -
Chandrawati Rona,
Olesen Morten T. J.,
Marini Thatiane C. C.,
Bisra Gurpal,
Guex Anne Géraldine,
de Oliveira Marcelo G.,
Zelikin Alexander N.,
Stevens Molly M.
Publication year - 2017
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201700385
Subject(s) - prodrug , liposome , enzyme , adept , chemistry , vinyl alcohol , cell encapsulation , pharmacology , materials science , cell , biochemistry , medicine , organic chemistry , polymer
Enzyme prodrug therapy (EPT) enables localized conversion of inert prodrugs to active drugs by enzymes. Performance of EPT necessitates that the enzyme remains active throughout the time frame of the envisioned therapeutic application. β‐glucuronidase is an enzyme with historically validated performance in EPT, however it retains its activity in biomaterials for an insufficiently long period of time, typically not exceeding 7 d. Herein, the encapsulation of β‐glucuronidase in liposomal subcompartments within poly(vinyl alcohol) electrospun fibers is reported, leading to the assembly of biocatalytically active materials with activity of the enzyme sustained over at least seven weeks. It is further shown that liposomes provide the highly beneficial stabilization of the enzyme when incubated in cell culture media. The assembled biocatalytic materials successfully produce antiproliferative drugs (SN‐38) using externally administered prodrugs (SN‐38‐glucuronide) and effectively suppress cell proliferation, with envisioned utility in the design of cardiovascular grafts.