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