Effect of cholesterol on nano-structural alteration of light-activatable liposomes via laser irradiation: Small angle neutron scattering study

Zheng Yuan; Saikat Das; Changwoo Do; Yoonjee C. Park

doi:10.1016/j.colsurfa.2022.128548

Effect of cholesterol on nano-structural alteration of light-activatable liposomes via laser irradiation: Small angle neutron scattering study

Zheng Yuan, Saikat Das, Changwoo Do, Yoonjee C. Park

SANS & Spin Echo

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Abstract

Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (–Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (–Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above T_c; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.

Original language	English
Article number	128548
Journal	Colloids and Surfaces A: Physicochemical and Engineering Aspects
Volume	641
DOIs	https://doi.org/10.1016/j.colsurfa.2022.128548
State	Published - May 20 2022

Funding

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoonjee Park reports financial support was provided by Ohio Lions Eye Research Foundation. Yoonjee Park reports financial support was provided by University of Cincinnati Center for Clinical and Translational Science. Yoonjee Park reports financial support was provided by National Eye Institute. This study was partially supported by AMD grant and Lois Hagelberger Huebner Young Investigator Award from Ohio Lions Eye Research Foundation, Office of Research at University of Cincinnati, CCTST, Cincinnati, Ohio and NIH ( R15 EY031500 ).

Funders	Funder number
CCTST
Office of Research at University of Cincinnati
National Institutes of Health	R15 EY031500
National Eye Institute
Advanced Micro Devices
Center for Clinical and Translational Science, University of Cincinnati
Ohio Lions Eye Research Foundation

Keywords

Cholesterol
Drug delivery
Laser-activated drug release
Light-activated liposomes
Neutron scattering

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10.1016/j.colsurfa.2022.128548

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title = "Effect of cholesterol on nano-structural alteration of light-activatable liposomes via laser irradiation: Small angle neutron scattering study",

abstract = "Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (–Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (–Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above Tc; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.",

keywords = "Cholesterol, Drug delivery, Laser-activated drug release, Light-activated liposomes, Neutron scattering",

author = "Zheng Yuan and Saikat Das and Changwoo Do and Park, {Yoonjee C.}",

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AU - Do, Changwoo

AU - Park, Yoonjee C.

PY - 2022/5/20

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N2 - Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (–Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (–Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above Tc; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.

AB - Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (–Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (–Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above Tc; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.

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Effect of cholesterol on nano-structural alteration of light-activatable liposomes via laser irradiation: Small angle neutron scattering study

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