Microfluidic generation of alginate microgels for the controlled delivery of lentivectors

Autor(es)

Madrigal, Justin L. ; Stilhano, Roberta S. ; Siltanen, Christian ; Tanaka, Kimberly ; Rezvani, Sabah N. ; Morgan, Ryan P. ; Revzin, Alexander ; Han, Sang W. ; Silva, Eduardo A.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MATERIALS CHEMISTRY B; v. 4, n. 43, p. 6989-6999, NOV 21 2016.
• Citações Web of Science: 10

Resumo

Lentivectors are widely used for gene delivery and have been increasingly tested in clinical trials. However, achieving safe, localized, and sufficient gene expression remain key challenges for effective lentivectoral therapy. Localized and efficient gene expression can be promoted by developing material systems to deliver lentivectors. Here, we address the utility of microgel encapsulation as a strategy for the controlled release of lentivectors. Three distinct routes for ionotropic gelation of alginate were incorporated into microfluidic templating to create lentivector-loaded microgels. Comparisons of the three microgels revealed marked differences in mechanical properties, crosslinking environment, and ultimately lentivector release and functional gene expression in vitro. Gelation with chelated calcium demonstrated low utility for gene delivery due to a loss of lentivector function with acidic gelation conditions. Both calcium carbonate gelation, and calcium chloride gelation, preserved lentivector function with a more sustained transduction and gene expression over 4 days observed with calcium chloride gelated microgels. The validation of these two strategies for lentivector microencapsulation may provide a platform for controlled gene delivery. (AU)

• Processo FAPESP: 12/00753-6 - Terapia gênica para redução de fibrose em modelo de ratos espontaneamente hipertensos
• Beneficiário: Roberta Sessa Stilhano Yamaguchi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/20206-8 - Modulação de monócitos, macrófagos e pericitos pelos genes dos fatores estimuladores de colônia para tratamento de isquemia de membros em modelo murino
• Beneficiário: Sang Won Han
• Modalidade de apoio: Auxílio à Pesquisa - Temático