Optimizing biodegradable nanoparticle size for tissue-specific delivery

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfluidics
  • Nanoparticles*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Tissue Distribution

Substances

  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer