Format

Send to

Choose Destination
J Control Release. 2019 Nov 28;314:92-101. doi: 10.1016/j.jconrel.2019.09.020. Epub 2019 Oct 22.

Optimizing biodegradable nanoparticle size for tissue-specific delivery.

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA.
2
Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA; Department of Therapeutic Radiology, Yale University, New Haven, CT, 06520, USA; Department of Genetics, Yale University, New Haven, CT, 06520, USA.
3
Department of Therapeutic Radiology, Yale University, New Haven, CT, 06520, USA.
4
Department of Therapeutic Radiology, Yale University, New Haven, CT, 06520, USA; Department of Genetics, Yale University, New Haven, CT, 06520, USA.
5
Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA; Department of Chemical & Environmental Engineering, Yale University, New Haven, CT, 06511, USA; Department of Physiology, Yale University, New Haven, CT, 06511, USA. Electronic address: mark.saltzman@yale.edu.

Abstract

Nanoparticles (NPs) are promising vehicles for drug delivery because of their potential to target specific tissues [1]. Although it is known that NP size plays a critical role in determining their biological activity, there are few quantitative studies of the role of NP size in determining biodistribution after systemic administration. Here, we engineered fluorescent, biodegradable poly(lactic-co-glycolic acid) (PLGA) NPs in a range of sizes (120-440nm) utilizing a microfluidic platform and used these NPs to determine the effect of diameter on bulk tissue and cellular distribution after systemic administration. We demonstrate that small NPs (∼120nm) exhibit enhanced uptake in bulk lung and bone marrow, while larger NPs are sequestered in the liver and spleen. We also show that small NPs (∼120nm) access specific alveolar cell populations and hematopoietic stem and progenitor cells more readily than larger NPs. Our results suggest that size of PLGA NPs can be used to tune delivery to certain tissues and cell populations in vivo.

KEYWORDS:

Biodegradable nanoparticles; Biodistribution; Nanomedicine; Poly(lactic-co-glycolic acid) (PLGA); Size; Targeting

PMID:
31654688
PMCID:
PMC6909251
[Available on 2020-11-28]
DOI:
10.1016/j.jconrel.2019.09.020

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center