Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery
This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery, but the...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2013
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| Online Access: | http://hdl.handle.net/1721.1/79048 |
| _version_ | 1826210588919857152 |
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| author | Poon, Zhiyong Lee, Jong Bum Morton, Stephen Winford Hammond, Paula T |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Poon, Zhiyong Lee, Jong Bum Morton, Stephen Winford Hammond, Paula T |
| author_sort | Poon, Zhiyong |
| collection | MIT |
| description | This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery, but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems; the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (9 h) and low accumulation (10–15% recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation. |
| first_indexed | 2024-09-23T14:52:03Z |
| format | Article |
| id | mit-1721.1/79048 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:52:03Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/790482022-09-29T11:05:25Z Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery Poon, Zhiyong Lee, Jong Bum Morton, Stephen Winford Hammond, Paula T Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Poon, Zhiyong Lee, Jong Bum Morton, Stephen Winford Hammond, Paula T. This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery, but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems; the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (9 h) and low accumulation (10–15% recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation. National Institutes of Health (U.S.) (NIBIB Grant R01EB008082) David H. Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies 2013-05-30T19:30:02Z 2013-05-30T19:30:02Z 2011-05 2011-04 Article http://purl.org/eprint/type/JournalArticle 1530-6984 1530-6992 http://hdl.handle.net/1721.1/79048 Poon, Zhiyong, Jong Bum Lee, Stephen W. Morton, and Paula T. Hammond. Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery. Nano Letters 11, no. 5 (May 11, 2011): 2096-2103. en_US http://dx.doi.org/10.1021/nl200636r Nano Letters Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society PMC |
| spellingShingle | Poon, Zhiyong Lee, Jong Bum Morton, Stephen Winford Hammond, Paula T Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery |
| title | Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery |
| title_full | Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery |
| title_fullStr | Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery |
| title_full_unstemmed | Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery |
| title_short | Controlling in Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery |
| title_sort | controlling in vivo stability and biodistribution in electrostatically assembled nanoparticles for systemic delivery |
| url | http://hdl.handle.net/1721.1/79048 |
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