Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective

Hypothesis: In conventional ‘bulk’ nanoprecipitation, the capacity to load hydrophobic drugs into the polymeric nanoparticles (NPs) is limited to about 1%. The size distribution of the resulting NPs becomes polydisperse when higher precursor concentration is used to increase the drug loading. Hence,...

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Main Authors: Cai, Truong H., Mandaric, Stefan, Chopra, Sunandini, Langer, Robert S, Karnik, Rohit
Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering
Format: Article
Language:English
Published: Elsevier BV 2020
Online Access:https://hdl.handle.net/1721.1/125309
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author Cai, Truong H.
Mandaric, Stefan
Chopra, Sunandini
Langer, Robert S
Karnik, Rohit
author2 Massachusetts Institute of Technology. Department of Chemical Engineering
author_facet Massachusetts Institute of Technology. Department of Chemical Engineering
Cai, Truong H.
Mandaric, Stefan
Chopra, Sunandini
Langer, Robert S
Karnik, Rohit
author_sort Cai, Truong H.
collection MIT
description Hypothesis: In conventional ‘bulk’ nanoprecipitation, the capacity to load hydrophobic drugs into the polymeric nanoparticles (NPs) is limited to about 1%. The size distribution of the resulting NPs becomes polydisperse when higher precursor concentration is used to increase the drug loading. Hence, it should be possible to enhance the hydrophobic drug loading in polymeric NPs while maintaining the uniform NP size distribution by optimizing the nanoprecipitation process and purification process. Experiments: Systematic studies were performed to enhance the loading of docetaxel (Dtxl) by using a process of centrifugal spin-down, rapid mixing by turbulence, and addition of co-solvent. The size distributions and Dtxl loading of the NPs were measured using dynamic light scattering and HPLC, respectively. Findings: The centrifugal spin-down process helps to maintain uniform size distribution even at the high precursor concentration. In bulk nanoprecipitation, the resulting NPs achieved Dtxl loading up to 3.2%. By adopting turbulence for rapid mixing, the loading of Dtxl increased to 4.4%. By adding hexane as co-solvent, the loading of Dtxl further increased to 5.5%. Because of the drug loading augmentation, high degree of control, and extremely high production rate, the developed method may be useful for industrial-scale production of personalized nanomedicines by nanoprecipitation.
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spelling mit-1721.1/1253092022-09-29T19:12:40Z Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective Cai, Truong H. Mandaric, Stefan Chopra, Sunandini Langer, Robert S Karnik, Rohit Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Hypothesis: In conventional ‘bulk’ nanoprecipitation, the capacity to load hydrophobic drugs into the polymeric nanoparticles (NPs) is limited to about 1%. The size distribution of the resulting NPs becomes polydisperse when higher precursor concentration is used to increase the drug loading. Hence, it should be possible to enhance the hydrophobic drug loading in polymeric NPs while maintaining the uniform NP size distribution by optimizing the nanoprecipitation process and purification process. Experiments: Systematic studies were performed to enhance the loading of docetaxel (Dtxl) by using a process of centrifugal spin-down, rapid mixing by turbulence, and addition of co-solvent. The size distributions and Dtxl loading of the NPs were measured using dynamic light scattering and HPLC, respectively. Findings: The centrifugal spin-down process helps to maintain uniform size distribution even at the high precursor concentration. In bulk nanoprecipitation, the resulting NPs achieved Dtxl loading up to 3.2%. By adopting turbulence for rapid mixing, the loading of Dtxl increased to 4.4%. By adding hexane as co-solvent, the loading of Dtxl further increased to 5.5%. Because of the drug loading augmentation, high degree of control, and extremely high production rate, the developed method may be useful for industrial-scale production of personalized nanomedicines by nanoprecipitation. National Institutes of Health (U.S.) (Grant EB015419) National Institutes of Health (U.S.) (Grant CA119349) Center of Cancer Nanotechnology Excellence at MIT-Harvard (National Cancer Institute (U.S.)) (Grant U54-CA151884) 2020-05-19T14:40:15Z 2020-05-19T14:40:15Z 2019-03 2020-03-17T16:35:01Z Article http://purl.org/eprint/type/JournalArticle 0021-9797 https://hdl.handle.net/1721.1/125309 Lim, Jong-Min et al. “Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective.” Journal of Colloid and Interface Science 538 (2019): 45-50 © 2019 The Author(s) en 10.1016/J.JCIS.2018.11.029 Journal of Colloid and Interface Science Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC
spellingShingle Cai, Truong H.
Mandaric, Stefan
Chopra, Sunandini
Langer, Robert S
Karnik, Rohit
Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective
title Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective
title_full Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective
title_fullStr Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective
title_full_unstemmed Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective
title_short Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective
title_sort drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer yong investigator perspective
url https://hdl.handle.net/1721.1/125309
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AT langerroberts drugloadingaugmentationinpolymericnanoparticlesusingacoaxialturbulentjetmixeryonginvestigatorperspective
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