2 research outputs found
Dendrimer-Inspired Nanomaterials for the <i>in Vivo</i> Delivery of siRNA to Lung Vasculature
Targeted RNA delivery to lung endothelial
cells has the potential to treat conditions that involve inflammation,
such as chronic asthma and obstructive pulmonary disease. To this
end, chemically modified dendrimer nanomaterials were synthesized
and optimized for targeted small interfering RNA (siRNA) delivery
to lung vasculature. Using a combinatorial approach, the free amines
on multigenerational poly(amido amine) and poly(propylenimine) dendrimers
were substituted with alkyl chains of increasing length. The top performing
materials from <i>in vivo</i> screens were found to primarily
target Tie2-expressing lung endothelial cells. At high doses, the
dendrimer–lipid derivatives did not cause chronic increases
in proinflammatory cytokines, and animals did not suffer weight loss
due to toxicity. We believe these materials have potential as agents
for the pulmonary delivery of RNA therapeutics
Dendrimer-Inspired Nanomaterials for the <i>in Vivo</i> Delivery of siRNA to Lung Vasculature
Targeted RNA delivery to lung endothelial
cells has the potential to treat conditions that involve inflammation,
such as chronic asthma and obstructive pulmonary disease. To this
end, chemically modified dendrimer nanomaterials were synthesized
and optimized for targeted small interfering RNA (siRNA) delivery
to lung vasculature. Using a combinatorial approach, the free amines
on multigenerational poly(amido amine) and poly(propylenimine) dendrimers
were substituted with alkyl chains of increasing length. The top performing
materials from <i>in vivo</i> screens were found to primarily
target Tie2-expressing lung endothelial cells. At high doses, the
dendrimer–lipid derivatives did not cause chronic increases
in proinflammatory cytokines, and animals did not suffer weight loss
due to toxicity. We believe these materials have potential as agents
for the pulmonary delivery of RNA therapeutics