Factors affecting the clearance and biodistribution of polymeric nanoparticles
Open accessAbstract
Nanoparticle (NP) drug delivery systems (5-250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.
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Spherical micelles of ~3-5 nm size are less probably to be taken up by macrophages due to minimum surface area and are excreted by the kidney.
“In general, spherical micelles of ~3–5 nm size are less probably to be taken up by the macrophages due to minimum surface area and are excreted by the kidney [90].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [90]
The ‘Effect of Surface Functionality and Charge’ section (page unavailable) reports that anionic micelles had reduced cellular uptake and that urinary excretion was their major excretion route. It attributes the reduced uptake to steric and electrostatic repulsion, not minimum surface area, and does not identify the micelles as spherical or approximately 3–5 nm in size. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCompared to neutral and negatively charged micelles, positively charged micelles are readily taken up by the RES due to increased interaction with the negatively charged cell membrane.
“Compared to neutral and negatively charged micelles, positively charged micelles are readily taken up by the RES due to increased interaction with the negatively charged cell membrane [90];”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [90]
The “Effect of Surface Functionality and Charge” section says positively charged nanoparticles have higher cellular uptake than neutral or negatively charged formulations, including uptake by phagocytic cells. Its micelle comparison addresses neutral and negatively charged micelles, not positively charged micelles; it also does not identify interaction with a negatively charged cell membrane as the mechanism. The claim therefore applies the general nanoparticle finding more specifically than the source supports. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNegatively charged micelles decrease the rate of cellular uptake and improve the blood circulation time.
“however, negatively charged micelles decrease the rate of cellular uptake and improve the blood circulation time.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [90]
The Effect of Surface Functionality and Charge section says lower liver and spleen accumulation of anionic micelles is believed to reflect decreased cellular uptake. But it also reports no remarkable difference in blood clearance kinetics between negatively charged and neutral micelles, so it does not support improved circulation time for the negatively charged micelles relative to neutral ones. (LLM, conf=0.88)
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- Authors
- Alexis, F., Pridgen, E., Molnar, L. K., & Farokhzad, O. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Alexis, Frank
- Farokhzad, Omid C.
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-08-01
- Volume
- 5
- Issue
- 4
- Pages
- 505-515
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC2663893
- OpenAlex
- W1516954147
- Cited by
- 3,699
- References
- 105
- Citations by year
- 2026: 169 · 2025: 181 · 2024: 169 · 2023: 215 · 2022: 221 · 2021: 221 · 2020: 292 · 2019: 261 · 2018: 241 · 2017: 265 · 2016: 293 · 2015: 239 · 2014: 220 · 2013: 226 · 2012: 205
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Pharmaceutics (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Applied Categorical Structures
- Funders
- Prostate Cancer Foundation
- National Institutes of Health (5u54ca119349-05, CA119349)
- National Cancer Institute (CA 119349, U54 CA-119349)
- National Institute of Biomedical Imaging and Bioengineering (K08EB003647, EB003647)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- polymeric nanoparticles, nanoparticle biodistribution, blood clearance, blood circulation half-life, nanoparticle drug delivery, surface modification, PEGylation, surface charge, targeting ligands, opsonization, organ-specific accumulation, nanoparticle size, nanoparticle composition
- MeSH terms
- Animals, Clinical Trials as Topic, Humans, Micelles, Particle Size, Surface Properties, Tissue Distribution, Nanoparticles
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