Microfluidic generation of alginate microgels for the controlled delivery of lentivectors

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6989-6999
Number of pages11
JournalJournal of Materials Chemistry B
Volume4
Issue number43
DOIs
StatePublished - 2016

Fingerprint

Microfluidics
Alginate
Gelation
Gene expression
Gene Expression
Calcium Chloride
Calcium chloride
Genes
Ionotropic gelation
Microencapsulation
Drug Compounding
Calcium Carbonate
Calcium carbonate
Encapsulation
Crosslinking
Calcium
Clinical Trials
Mechanical properties
alginic acid
Therapeutics

ASJC Scopus subject areas

  • Chemistry(all)
  • Medicine(all)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Madrigal, J. L., Stilhano, R. S., Siltanen, C., Tanaka, K., Rezvani, S. N., Morgan, R. P., ... Silva, E. (2016). Microfluidic generation of alginate microgels for the controlled delivery of lentivectors. Journal of Materials Chemistry B, 4(43), 6989-6999. https://doi.org/10.1039/c6tb02150f

Microfluidic generation of alginate microgels for the controlled delivery of lentivectors. / Madrigal, Justin L.; Stilhano, Roberta S.; Siltanen, Christian; Tanaka, Kimberly; Rezvani, Sabah N.; Morgan, Ryan P.; Revzin, Alexander; Han, Sang W.; Silva, Eduardo.

In: Journal of Materials Chemistry B, Vol. 4, No. 43, 2016, p. 6989-6999.

Research output: Contribution to journalArticle

Madrigal, JL, Stilhano, RS, Siltanen, C, Tanaka, K, Rezvani, SN, Morgan, RP, Revzin, A, Han, SW & Silva, E 2016, 'Microfluidic generation of alginate microgels for the controlled delivery of lentivectors', Journal of Materials Chemistry B, vol. 4, no. 43, pp. 6989-6999. https://doi.org/10.1039/c6tb02150f
Madrigal, Justin L. ; Stilhano, Roberta S. ; Siltanen, Christian ; Tanaka, Kimberly ; Rezvani, Sabah N. ; Morgan, Ryan P. ; Revzin, Alexander ; Han, Sang W. ; Silva, Eduardo. / Microfluidic generation of alginate microgels for the controlled delivery of lentivectors. In: Journal of Materials Chemistry B. 2016 ; Vol. 4, No. 43. pp. 6989-6999.
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