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 Geraldine ; de Oliveira, Marcelo G. ; Zelikin, Alexander N. ; Stevens, Molly M.

• Document type: Journal article
• Source: ADVANCED HEALTHCARE MATERIALS; v. 6, n. 17 SEP 6 2017.
• Web of Science Citations: 11

Abstract

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. beta-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 beta-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. (AU)

• FAPESP's process: 14/03266-4 - PVA-F-127 thermosensitive nanocarriers for the photochemical nitric oxide release
• Grantee: Thatiane Cristine Camargo Marini
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/13290-2 - 27th European Conference on Biomaterials
• Grantee: Marcelo Ganzarolli de Oliveira
• Support Opportunities: Research Grants - Meeting - Abroad