Optimizing biodegradable nanoparticle size for tissue-specific delivery

JOURNAL OF CONTROLLED RELEASE

卷:314

Article

Mandl, Hanna K.¹  Quijano, Elias^1,4,5  Suh, Hee Won¹  Sparago, Emily¹  Oeck, Sebastian⁴  Grun, Molly¹  Glazer, Peter M.^4,5  Saltzman, W. Mark^1,2,3 

[1] Yale Univ, Dept Biomed Engn, New Haven, CT 06511 USA

[2] Yale Univ, Dept Chem & Environm Engn, New Haven, CT 06511 USA

[3] Yale Univ, Dept Physiol, New Haven, CT 06511 USA

[4] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06520 USA

[5] Yale Univ, Dept Genet, New Haven, CT 06520 USA

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

DOI  :  10.1016/j.jconrel.2019.09.020

来源: Elsevier

【 摘 要 】

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 (120-440 nm) 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 (similar to 120 nm) 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 (similar to 120 nm) 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.

【 授权许可】

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