Precise control of liposome size using characteristic time depends on solvent type and membrane properties
Abstract Controlling the sizes of liposomes is critical in drug delivery systems because it directly influences their cellular uptake, transportation, and accumulation behavior. Although hydrodynamic focusing has frequently been employed when synthesizing nano-sized liposomes, little is known regard...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2023-03-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-023-31895-z |
_version_ | 1797274534023266304 |
---|---|
author | Sunghak Choi Bongsu Kang Eunhye Yang Keesung Kim Moon Kyu Kwak Pahn-Shick Chang Ho-Sup Jung |
author_facet | Sunghak Choi Bongsu Kang Eunhye Yang Keesung Kim Moon Kyu Kwak Pahn-Shick Chang Ho-Sup Jung |
author_sort | Sunghak Choi |
collection | DOAJ |
description | Abstract Controlling the sizes of liposomes is critical in drug delivery systems because it directly influences their cellular uptake, transportation, and accumulation behavior. Although hydrodynamic focusing has frequently been employed when synthesizing nano-sized liposomes, little is known regarding how flow characteristics determine liposome formation. Here, various sizes of homogeneous liposomes (50–400 nm) were prepared according to flow rate ratios in two solvents, ethanol, and isopropyl alcohol (IPA). Relatively small liposomes formed in ethanol due to its low viscosity and high diffusivity, whereas larger, more poly-dispersed liposomes formed when using IPA as a solvent. This difference was investigated via numerical simulations using the characteristic time factor to predict the liposome size; this approach was also used to examine the flow characteristics inside the microfluidic channel. In case of the liposomes, the membrane rigidity also has a critical role in determining their size. The increased viscosity and packing density of the membrane by addition of cholesterol confirmed by fluorescence anisotropy and polarity lead to increase in liposome size (40–530 nm). However, the interposition of short-chain lipids de-aligned the bilayer membrane, leading to its degradation; this decreased the liposome size. Adding short-chain lipids linearly decreased the liposome size (130–230 nm), but at a shallower gradient than that of cholesterol. This analytical study expands the understanding of microfluidic environment in the liposome synthesis by offering design parameters and their relation to the size of liposomes. |
first_indexed | 2024-03-07T14:59:46Z |
format | Article |
id | doaj.art-c4e7e62a23b9476f9cf5997368c28f10 |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-03-07T14:59:46Z |
publishDate | 2023-03-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Scientific Reports |
spelling | doaj.art-c4e7e62a23b9476f9cf5997368c28f102024-03-05T19:13:56ZengNature PortfolioScientific Reports2045-23222023-03-0113111210.1038/s41598-023-31895-zPrecise control of liposome size using characteristic time depends on solvent type and membrane propertiesSunghak Choi0Bongsu Kang1Eunhye Yang2Keesung Kim3Moon Kyu Kwak4Pahn-Shick Chang5Ho-Sup Jung6Center for Food and Bioconvergence, Department of Food Science and Biotechnology, Seoul National UniversityCenter for Food and Bioconvergence, Department of Food Science and Biotechnology, Seoul National UniversityDepartment of Agricultural Biotechnology, Seoul National UniversityResearch Inst. of Advanced. Materials, Collage of Engineering, Seoul National UniversitySchool of Mechanical Engineering, Kyungpook National UniversityCenter for Food and Bioconvergence, Department of Food Science and Biotechnology, Seoul National UniversityCenter for Food and Bioconvergence, Department of Food Science and Biotechnology, Seoul National UniversityAbstract Controlling the sizes of liposomes is critical in drug delivery systems because it directly influences their cellular uptake, transportation, and accumulation behavior. Although hydrodynamic focusing has frequently been employed when synthesizing nano-sized liposomes, little is known regarding how flow characteristics determine liposome formation. Here, various sizes of homogeneous liposomes (50–400 nm) were prepared according to flow rate ratios in two solvents, ethanol, and isopropyl alcohol (IPA). Relatively small liposomes formed in ethanol due to its low viscosity and high diffusivity, whereas larger, more poly-dispersed liposomes formed when using IPA as a solvent. This difference was investigated via numerical simulations using the characteristic time factor to predict the liposome size; this approach was also used to examine the flow characteristics inside the microfluidic channel. In case of the liposomes, the membrane rigidity also has a critical role in determining their size. The increased viscosity and packing density of the membrane by addition of cholesterol confirmed by fluorescence anisotropy and polarity lead to increase in liposome size (40–530 nm). However, the interposition of short-chain lipids de-aligned the bilayer membrane, leading to its degradation; this decreased the liposome size. Adding short-chain lipids linearly decreased the liposome size (130–230 nm), but at a shallower gradient than that of cholesterol. This analytical study expands the understanding of microfluidic environment in the liposome synthesis by offering design parameters and their relation to the size of liposomes.https://doi.org/10.1038/s41598-023-31895-z |
spellingShingle | Sunghak Choi Bongsu Kang Eunhye Yang Keesung Kim Moon Kyu Kwak Pahn-Shick Chang Ho-Sup Jung Precise control of liposome size using characteristic time depends on solvent type and membrane properties Scientific Reports |
title | Precise control of liposome size using characteristic time depends on solvent type and membrane properties |
title_full | Precise control of liposome size using characteristic time depends on solvent type and membrane properties |
title_fullStr | Precise control of liposome size using characteristic time depends on solvent type and membrane properties |
title_full_unstemmed | Precise control of liposome size using characteristic time depends on solvent type and membrane properties |
title_short | Precise control of liposome size using characteristic time depends on solvent type and membrane properties |
title_sort | precise control of liposome size using characteristic time depends on solvent type and membrane properties |
url | https://doi.org/10.1038/s41598-023-31895-z |
work_keys_str_mv | AT sunghakchoi precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties AT bongsukang precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties AT eunhyeyang precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties AT keesungkim precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties AT moonkyukwak precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties AT pahnshickchang precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties AT hosupjung precisecontrolofliposomesizeusingcharacteristictimedependsonsolventtypeandmembraneproperties |