Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media

Research output: Contribution to journalJournal articlepeer-review

Standard

Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media. / Mertz, Nina; Yaghmur, Anan; Østergaard, Jesper; Amenitsch, Heinz; Larsen, Susan Weng.

In: Journal of Colloid and Interface Science, Vol. 602, 2021, p. 415-425.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Mertz, N, Yaghmur, A, Østergaard, J, Amenitsch, H & Larsen, SW 2021, 'Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media', Journal of Colloid and Interface Science, vol. 602, pp. 415-425. https://doi.org/10.1016/j.jcis.2021.06.031

APA

Mertz, N., Yaghmur, A., Østergaard, J., Amenitsch, H., & Larsen, S. W. (2021). Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media. Journal of Colloid and Interface Science, 602, 415-425. https://doi.org/10.1016/j.jcis.2021.06.031

Vancouver

Mertz N, Yaghmur A, Østergaard J, Amenitsch H, Larsen SW. Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media. Journal of Colloid and Interface Science. 2021;602:415-425. https://doi.org/10.1016/j.jcis.2021.06.031

Author

Mertz, Nina ; Yaghmur, Anan ; Østergaard, Jesper ; Amenitsch, Heinz ; Larsen, Susan Weng. / Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media. In: Journal of Colloid and Interface Science. 2021 ; Vol. 602. pp. 415-425.

Bibtex

@article{92d87676d57b4e7092e7ad5a6d6d2324,
title = "Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media",
abstract = "Formation of high viscous inverse lyotropic liquid crystalline phases in situ upon exposure of low viscous drug-loaded lipid preformulations to synovial fluid provides a promising approach for design of depot formulations for intra-articular drug delivery. Rational formulation design relies on a fundamental understanding of the synovial fluid-mediated dynamic structural transitions occurring at the administration site. At conditions mimicking the in vivo situation, we investigated in real-time such transitions at multiple positions by synchrotron small-angle X-ray scattering (SAXS) combined with an injection-cell. An injectable diclofenac-loaded quaternary preformulation consisting of 72/8/10/10% (w/w) glycerol monooleate/1,2-dioleoyl-glycero-3-phospho-rac-(1-glycerol)/ethanol/water was injected into hyaluronic acid solution or synovial fluid. A fast generation of a coherent drug depot of inverse bicontinuous Im3m and Pn3m cubic phases was observed. Through construction of 2D spatial maps from measurements performed 60 min after injection of the preformulation, it was possible to differentiate liquid crystalline rich- and excess hyaluronic acid solution- or synovial fluid-rich regimes. Synchrotron SAXS findings confirmed that the exposure of the preformulation to the media leads to alterations in structural features in position- and time-dependent manners. Effects of biologically relevant medium composition on the structural features, and implications for development of formulations with sustained drug release properties are highlighted.",
keywords = "In vitro release, Intra-articular administration, Inverse bicontinuous cubic phases, Non-lamellar liquid crystalline phases, Sustained drug release, Synchrotron SAXS, Synovial fluid",
author = "Nina Mertz and Anan Yaghmur and Jesper {\O}stergaard and Heinz Amenitsch and Larsen, {Susan Weng}",
note = "Funding Information: This project has received a grant from the Br{\o}drene Hartmann Foundation (Copenhagen, Denmark). SAXS beamtime at the synchrotron light source ELETTRA (Trieste, Italy) was provided under the proposal 20182095 . The authors are grateful for the assistance of the beamline staff. The authors acknowledge the proficient assistance of Gizem Bor (Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen ) during SAXS investigations. Funding Information: This project has received a grant from the Br?drene Hartmann Foundation (Copenhagen, Denmark). SAXS beamtime at the synchrotron light source ELETTRA (Trieste, Italy) was provided under the proposal 20182095. The authors are grateful for the assistance of the beamline staff. The authors acknowledge the proficient assistance of Gizem Bor (Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen) during SAXS investigations. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
doi = "10.1016/j.jcis.2021.06.031",
language = "English",
volume = "602",
pages = "415--425",
journal = "Journal of Colloid and Interface Science",
issn = "0021-9797",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - Spatially and time-resolved SAXS for monitoring dynamic structural transitions during in situ generation of non-lamellar liquid crystalline phases in biologically relevant media

AU - Mertz, Nina

AU - Yaghmur, Anan

AU - Østergaard, Jesper

AU - Amenitsch, Heinz

AU - Larsen, Susan Weng

N1 - Funding Information: This project has received a grant from the Brødrene Hartmann Foundation (Copenhagen, Denmark). SAXS beamtime at the synchrotron light source ELETTRA (Trieste, Italy) was provided under the proposal 20182095 . The authors are grateful for the assistance of the beamline staff. The authors acknowledge the proficient assistance of Gizem Bor (Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen ) during SAXS investigations. Funding Information: This project has received a grant from the Br?drene Hartmann Foundation (Copenhagen, Denmark). SAXS beamtime at the synchrotron light source ELETTRA (Trieste, Italy) was provided under the proposal 20182095. The authors are grateful for the assistance of the beamline staff. The authors acknowledge the proficient assistance of Gizem Bor (Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen) during SAXS investigations. Publisher Copyright: © 2021

PY - 2021

Y1 - 2021

N2 - Formation of high viscous inverse lyotropic liquid crystalline phases in situ upon exposure of low viscous drug-loaded lipid preformulations to synovial fluid provides a promising approach for design of depot formulations for intra-articular drug delivery. Rational formulation design relies on a fundamental understanding of the synovial fluid-mediated dynamic structural transitions occurring at the administration site. At conditions mimicking the in vivo situation, we investigated in real-time such transitions at multiple positions by synchrotron small-angle X-ray scattering (SAXS) combined with an injection-cell. An injectable diclofenac-loaded quaternary preformulation consisting of 72/8/10/10% (w/w) glycerol monooleate/1,2-dioleoyl-glycero-3-phospho-rac-(1-glycerol)/ethanol/water was injected into hyaluronic acid solution or synovial fluid. A fast generation of a coherent drug depot of inverse bicontinuous Im3m and Pn3m cubic phases was observed. Through construction of 2D spatial maps from measurements performed 60 min after injection of the preformulation, it was possible to differentiate liquid crystalline rich- and excess hyaluronic acid solution- or synovial fluid-rich regimes. Synchrotron SAXS findings confirmed that the exposure of the preformulation to the media leads to alterations in structural features in position- and time-dependent manners. Effects of biologically relevant medium composition on the structural features, and implications for development of formulations with sustained drug release properties are highlighted.

AB - Formation of high viscous inverse lyotropic liquid crystalline phases in situ upon exposure of low viscous drug-loaded lipid preformulations to synovial fluid provides a promising approach for design of depot formulations for intra-articular drug delivery. Rational formulation design relies on a fundamental understanding of the synovial fluid-mediated dynamic structural transitions occurring at the administration site. At conditions mimicking the in vivo situation, we investigated in real-time such transitions at multiple positions by synchrotron small-angle X-ray scattering (SAXS) combined with an injection-cell. An injectable diclofenac-loaded quaternary preformulation consisting of 72/8/10/10% (w/w) glycerol monooleate/1,2-dioleoyl-glycero-3-phospho-rac-(1-glycerol)/ethanol/water was injected into hyaluronic acid solution or synovial fluid. A fast generation of a coherent drug depot of inverse bicontinuous Im3m and Pn3m cubic phases was observed. Through construction of 2D spatial maps from measurements performed 60 min after injection of the preformulation, it was possible to differentiate liquid crystalline rich- and excess hyaluronic acid solution- or synovial fluid-rich regimes. Synchrotron SAXS findings confirmed that the exposure of the preformulation to the media leads to alterations in structural features in position- and time-dependent manners. Effects of biologically relevant medium composition on the structural features, and implications for development of formulations with sustained drug release properties are highlighted.

KW - In vitro release

KW - Intra-articular administration

KW - Inverse bicontinuous cubic phases

KW - Non-lamellar liquid crystalline phases

KW - Sustained drug release

KW - Synchrotron SAXS

KW - Synovial fluid

U2 - 10.1016/j.jcis.2021.06.031

DO - 10.1016/j.jcis.2021.06.031

M3 - Journal article

C2 - 34144300

AN - SCOPUS:85107986433

VL - 602

SP - 415

EP - 425

JO - Journal of Colloid and Interface Science

JF - Journal of Colloid and Interface Science

SN - 0021-9797

ER -

ID: 273634035