Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes for Controlled, Localized Synthesis of Therapeutics

Autor(es)

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.

• Tipo de documento: Artigo Científico
• Fonte: ADVANCED HEALTHCARE MATERIALS; v. 6, n. 17 SEP 6 2017.
• Citações Web of Science: 11

Resumo

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)

• Processo FAPESP: 14/03266-4 - Nanocarregadores termosensíveis de PVA-F-127 para a liberação fotoquímica de óxido nítrico
• Beneficiário: Thatiane Cristine Camargo Marini
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/13290-2 - 27th European Conference on Biomaterials
• Beneficiário: Marcelo Ganzarolli de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Reunião - Exterior