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Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles
PURPOSE: Evaluate fundamental parameters that dictate the effectiveness of drug loading. METHODS: A model water-soluble drug lacking ionizable groups, pirfenidone (PFD), was encapsulated through nanoprecipitation in poly(ethylene glycol)-poly(lactic acid) (PEG-PLA)-poly(lactic-co-glycolic acid) (PLG...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040083/ https://www.ncbi.nlm.nih.gov/pubmed/32095934 http://dx.doi.org/10.1007/s11095-020-2783-4 |
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author | Maslanka Figueroa, Sara Fleischmann, Daniel Beck, Sebastian Goepferich, Achim |
author_facet | Maslanka Figueroa, Sara Fleischmann, Daniel Beck, Sebastian Goepferich, Achim |
author_sort | Maslanka Figueroa, Sara |
collection | PubMed |
description | PURPOSE: Evaluate fundamental parameters that dictate the effectiveness of drug loading. METHODS: A model water-soluble drug lacking ionizable groups, pirfenidone (PFD), was encapsulated through nanoprecipitation in poly(ethylene glycol)-poly(lactic acid) (PEG-PLA)-poly(lactic-co-glycolic acid) (PLGA) NPs. Firstly, the thermodynamic parameters predicting drug-polymer miscibility were determined to assess the system’s suitability. Then, the encapsulation was evaluated experimentally by two different techniques, bulk and microfluidic (MF) nanoprecipitation. Additionally, the number of molecules that fit in a particle core were calculated and the loading determined experimentally for different core sizes. Lastly, the effect of co-encapsulation of α-lipoic acid (LA), a drug with complementary therapeutic effects and enhanced lipophilicity, was evaluated. RESULTS: The thermodynamic miscibility parameters predicted a good suitability of the selected system. MF manufacturing enhanced the encapsulation efficiency by 60–90% and achieved a 2-fold higher NP cellular uptake. Considering spatial constrictions for drug encapsulation and increasing the size of the PLGA core the number of PFD molecules per NP was raised from under 500 to up to 2000. More so, the co-encapsulation of LA increased the number of drug molecules per particle by 96%, with no interference with the release profile. CONCLUSIONS: Thermodynamic, spatial and methodological parameters should be considered to optimize drug encapsulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-2783-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7040083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-70400832020-03-10 Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles Maslanka Figueroa, Sara Fleischmann, Daniel Beck, Sebastian Goepferich, Achim Pharm Res Research Paper PURPOSE: Evaluate fundamental parameters that dictate the effectiveness of drug loading. METHODS: A model water-soluble drug lacking ionizable groups, pirfenidone (PFD), was encapsulated through nanoprecipitation in poly(ethylene glycol)-poly(lactic acid) (PEG-PLA)-poly(lactic-co-glycolic acid) (PLGA) NPs. Firstly, the thermodynamic parameters predicting drug-polymer miscibility were determined to assess the system’s suitability. Then, the encapsulation was evaluated experimentally by two different techniques, bulk and microfluidic (MF) nanoprecipitation. Additionally, the number of molecules that fit in a particle core were calculated and the loading determined experimentally for different core sizes. Lastly, the effect of co-encapsulation of α-lipoic acid (LA), a drug with complementary therapeutic effects and enhanced lipophilicity, was evaluated. RESULTS: The thermodynamic miscibility parameters predicted a good suitability of the selected system. MF manufacturing enhanced the encapsulation efficiency by 60–90% and achieved a 2-fold higher NP cellular uptake. Considering spatial constrictions for drug encapsulation and increasing the size of the PLGA core the number of PFD molecules per NP was raised from under 500 to up to 2000. More so, the co-encapsulation of LA increased the number of drug molecules per particle by 96%, with no interference with the release profile. CONCLUSIONS: Thermodynamic, spatial and methodological parameters should be considered to optimize drug encapsulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-2783-4) contains supplementary material, which is available to authorized users. Springer US 2020-02-24 2020 /pmc/articles/PMC7040083/ /pubmed/32095934 http://dx.doi.org/10.1007/s11095-020-2783-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Paper Maslanka Figueroa, Sara Fleischmann, Daniel Beck, Sebastian Goepferich, Achim Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles |
title | Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles |
title_full | Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles |
title_fullStr | Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles |
title_full_unstemmed | Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles |
title_short | Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles |
title_sort | thermodynamic, spatial and methodological considerations for the manufacturing of therapeutic polymer nanoparticles |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040083/ https://www.ncbi.nlm.nih.gov/pubmed/32095934 http://dx.doi.org/10.1007/s11095-020-2783-4 |
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