Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration

<b>Background/Objectives:</b> Hydrophobic microparticles are one of the most versatile structures in drug delivery and tissue engineering. These constructs offer a protective environment for hydrophobic or water-sensitive compounds (e.g., drugs, peroxides), providing an optimal solution...

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Main Authors: Francisca L. Gomes, Francisco Conceição, Liliana Moreira Teixeira, Jeroen Leijten, Pascal Jonkheijm
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/64
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author Francisca L. Gomes
Francisco Conceição
Liliana Moreira Teixeira
Jeroen Leijten
Pascal Jonkheijm
author_facet Francisca L. Gomes
Francisco Conceição
Liliana Moreira Teixeira
Jeroen Leijten
Pascal Jonkheijm
author_sort Francisca L. Gomes
collection DOAJ
description <b>Background/Objectives:</b> Hydrophobic microparticles are one of the most versatile structures in drug delivery and tissue engineering. These constructs offer a protective environment for hydrophobic or water-sensitive compounds (e.g., drugs, peroxides), providing an optimal solution for numerous biomedical purposes, such as drug delivery or oxygen therapeutics. The intravascular administration of hydrophobic microparticles requires a safe-to-flow particle profile, which typically corresponds to a maximum size of 5 µm—the generally accepted diameter for the thinnest blood vessels in humans. However, the production of hydrophobic microparticles below this size range remains largely unexplored. In this work, we investigate the fabrication of hydrophobic microparticles at safe-to-inject and safe-to-flow sizes (<5 µm) for intravascular administration. <b>Methods:</b> Polycaprolactone microparticles (PCL MPs) are produced using a double-emulsification method with tip ultrasonication, for which various production parameters (PCL molecular weight, PCL concentration, type of stabilizer, and filtration) are optimized to obtain particles at sizes below 5 µm. <b>Results:</b> We achieve a PCL MP size distribution of 99.8% below this size limit, and prove that these particles can flow without obstruction through a microfluidic model emulating a thin human blood capillary (4.1 µm × 3.0 µm width × heigh). <b>Conclusions:</b> Overall, we demonstrate that hydrophobic microparticles can be fabricated at safe-to-flow sizes using a simple and scalable setup, paving the way towards their applicability as new intravascular injectables.
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spelling doaj-art-063465fb4f204f4686baf2007f7b8ee92025-01-24T13:45:47ZengMDPI AGPharmaceutics1999-49232025-01-011716410.3390/pharmaceutics17010064Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular AdministrationFrancisca L. Gomes0Francisco Conceição1Liliana Moreira Teixeira2Jeroen Leijten3Pascal Jonkheijm4Laboratory of Biointerface Chemistry, Department of Molecules and Materials, Faculty of Science and Technology, Technical Medical Centre and MESA+ Institute, University of Twente, 7522NB Enschede, The NetherlandsDepartment of BioEngineering Technologies, Advanced Organ Bioengineering and Therapeutics, Faculty of Science and Technology, Technical Medical Centre, University of Twente, 7522NB Enschede, The NetherlandsDepartment of BioEngineering Technologies, Advanced Organ Bioengineering and Therapeutics, Faculty of Science and Technology, Technical Medical Centre, University of Twente, 7522NB Enschede, The NetherlandsLeijten Laboratory, Department of BioEngineering Technologies, Faculty of Science and Technology, Technical Medical Centre, University of Twente, 7522NB Enschede, The NetherlandsLaboratory of Biointerface Chemistry, Department of Molecules and Materials, Faculty of Science and Technology, Technical Medical Centre and MESA+ Institute, University of Twente, 7522NB Enschede, The Netherlands<b>Background/Objectives:</b> Hydrophobic microparticles are one of the most versatile structures in drug delivery and tissue engineering. These constructs offer a protective environment for hydrophobic or water-sensitive compounds (e.g., drugs, peroxides), providing an optimal solution for numerous biomedical purposes, such as drug delivery or oxygen therapeutics. The intravascular administration of hydrophobic microparticles requires a safe-to-flow particle profile, which typically corresponds to a maximum size of 5 µm—the generally accepted diameter for the thinnest blood vessels in humans. However, the production of hydrophobic microparticles below this size range remains largely unexplored. In this work, we investigate the fabrication of hydrophobic microparticles at safe-to-inject and safe-to-flow sizes (<5 µm) for intravascular administration. <b>Methods:</b> Polycaprolactone microparticles (PCL MPs) are produced using a double-emulsification method with tip ultrasonication, for which various production parameters (PCL molecular weight, PCL concentration, type of stabilizer, and filtration) are optimized to obtain particles at sizes below 5 µm. <b>Results:</b> We achieve a PCL MP size distribution of 99.8% below this size limit, and prove that these particles can flow without obstruction through a microfluidic model emulating a thin human blood capillary (4.1 µm × 3.0 µm width × heigh). <b>Conclusions:</b> Overall, we demonstrate that hydrophobic microparticles can be fabricated at safe-to-flow sizes using a simple and scalable setup, paving the way towards their applicability as new intravascular injectables.https://www.mdpi.com/1999-4923/17/1/64microparticlespolycaprolactoneemulsificationinjectabilityblood capillary
spellingShingle Francisca L. Gomes
Francisco Conceição
Liliana Moreira Teixeira
Jeroen Leijten
Pascal Jonkheijm
Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
Pharmaceutics
microparticles
polycaprolactone
emulsification
injectability
blood capillary
title Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
title_full Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
title_fullStr Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
title_full_unstemmed Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
title_short Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
title_sort production of hydrophobic microparticles at safe to inject sizes for intravascular administration
topic microparticles
polycaprolactone
emulsification
injectability
blood capillary
url https://www.mdpi.com/1999-4923/17/1/64
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