Microfluidic generation of alginate microgels for the controlled delivery of lentivectors

Author(s)

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

• Document type: Journal article
• Source: JOURNAL OF MATERIALS CHEMISTRY B; v. 4, n. 43, p. 6989-6999, NOV 21 2016.
• Web of Science Citations: 10

Abstract

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)

• FAPESP's process: 12/00753-6 - GENE THERAPY FOR REDUCTION OF FIBROSIS IN A MODEL OF SPONTENOUSLY HYPERTENSIVE RATS
• Grantee: Roberta Sessa Stilhano Yamaguchi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia
• Grantee: Sang Won Han
• Support Opportunities: Research Projects - Thematic Grants