The architecture and biological performance of drug-loaded LbL nanoparticles
Layer-by-Layer (LbL) nanoparticles are an emerging class of therapeutic carriers that afford precise control over key design parameters that facilitate improved drug and carrier pharmacokinetics, and enhanced molecular-targeting capabilities. This paper advances the development of these systems by e...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101186 |
| _version_ | 1826209385113714688 |
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| author | Morton, Stephen Winford Poon, Zhiyong Hammond, Paula T |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Morton, Stephen Winford Poon, Zhiyong Hammond, Paula T |
| author_sort | Morton, Stephen Winford |
| collection | MIT |
| description | Layer-by-Layer (LbL) nanoparticles are an emerging class of therapeutic carriers that afford precise control over key design parameters that facilitate improved drug and carrier pharmacokinetics, and enhanced molecular-targeting capabilities. This paper advances the development of these systems by establishing them as drug carriers, with the means to control drug release in a systemic environment and retard particle clearance from circulation, promoting improved biodistribution of the drug-containing system. Using dual-fluorescent tracking in vivo, this work establishes a robust means of screening libraries of LbL systems generated, affording simultaneous resolution over persistence and biodistribution of both the drug and carrier following systemic administration of a single particle formulation. Employing a PLGA drug-containing core as a substrate for LbL deposition, a range of coated systems were fabricated to investigate the abilities of these films to stabilize drug for delivery as well as to improve the pharmacokinetics of both the drug and carrier. Significant reductions in liver accumulation were observed for different formulations of the layered architectures within the first 30 min of systemic circulation. LbL architectures diminished liver localization of the surrogate drug, cardiogreen, by 10–25% ID/g relative to native PLGA nanoparticles and modulated carrier accumulation in the liver >50% ID/g. Further, enhanced persistence of the drug was observed with the coated systems, significantly increasing the drug half-life from 2 to 3 min for free drug and 1.87 h for the uncoated core to 4.17 h and 4.54 h for the coated systems. These systems provide an exciting, modular platform that improves the pharmacokinetic properties of the therapeutic, reduces bolus release of drug from nanoparticles, and enhances the safety and circulation half-life of the drug in vivo, proving them to be highly clinically-relevant and a promising approach for future development of molecularly-targeted and combination therapeutics. |
| first_indexed | 2024-09-23T14:21:41Z |
| format | Article |
| id | mit-1721.1/101186 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:21:41Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1011862022-10-01T20:50:32Z The architecture and biological performance of drug-loaded LbL nanoparticles Morton, Stephen Winford Poon, Zhiyong Hammond, Paula T Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Morton, Stephen Winford Poon, Zhiyong Hammond, Paula T. Layer-by-Layer (LbL) nanoparticles are an emerging class of therapeutic carriers that afford precise control over key design parameters that facilitate improved drug and carrier pharmacokinetics, and enhanced molecular-targeting capabilities. This paper advances the development of these systems by establishing them as drug carriers, with the means to control drug release in a systemic environment and retard particle clearance from circulation, promoting improved biodistribution of the drug-containing system. Using dual-fluorescent tracking in vivo, this work establishes a robust means of screening libraries of LbL systems generated, affording simultaneous resolution over persistence and biodistribution of both the drug and carrier following systemic administration of a single particle formulation. Employing a PLGA drug-containing core as a substrate for LbL deposition, a range of coated systems were fabricated to investigate the abilities of these films to stabilize drug for delivery as well as to improve the pharmacokinetics of both the drug and carrier. Significant reductions in liver accumulation were observed for different formulations of the layered architectures within the first 30 min of systemic circulation. LbL architectures diminished liver localization of the surrogate drug, cardiogreen, by 10–25% ID/g relative to native PLGA nanoparticles and modulated carrier accumulation in the liver >50% ID/g. Further, enhanced persistence of the drug was observed with the coated systems, significantly increasing the drug half-life from 2 to 3 min for free drug and 1.87 h for the uncoated core to 4.17 h and 4.54 h for the coated systems. These systems provide an exciting, modular platform that improves the pharmacokinetic properties of the therapeutic, reduces bolus release of drug from nanoparticles, and enhances the safety and circulation half-life of the drug in vivo, proving them to be highly clinically-relevant and a promising approach for future development of molecularly-targeted and combination therapeutics. Janssen Pharmaceutical Ltd. (TRANSCEND Partnership) National Science Foundation (U.S.). Graduate Research Fellowship 2016-02-16T14:07:46Z 2016-02-16T14:07:46Z 2013-04 2013-02 Article http://purl.org/eprint/type/JournalArticle 01429612 1878-5905 http://hdl.handle.net/1721.1/101186 Morton, Stephen W., Zhiyong Poon, and Paula T. Hammond. “The Architecture and Biological Performance of Drug-Loaded LbL Nanoparticles.” Biomaterials 34, no. 21 (July 2013): 5328–35. en_US http://dx.doi.org/10.1016/j.biomaterials.2013.03.059 Biomaterials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Morton, Stephen Winford Poon, Zhiyong Hammond, Paula T The architecture and biological performance of drug-loaded LbL nanoparticles |
| title | The architecture and biological performance of drug-loaded LbL nanoparticles |
| title_full | The architecture and biological performance of drug-loaded LbL nanoparticles |
| title_fullStr | The architecture and biological performance of drug-loaded LbL nanoparticles |
| title_full_unstemmed | The architecture and biological performance of drug-loaded LbL nanoparticles |
| title_short | The architecture and biological performance of drug-loaded LbL nanoparticles |
| title_sort | architecture and biological performance of drug loaded lbl nanoparticles |
| url | http://hdl.handle.net/1721.1/101186 |
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