期刊
JOURNAL OF COLLOID AND INTERFACE SCIENCE
卷 582, 期 -, 页码 773-781出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2020.08.084
关键词
Albumin; Lyotropic liquid crystals; Inverse bicontinuous cubic phase; Inverse hexagonal phase; In situ forming drug delivery systems; Stimulus-responsive precursors; Synchrotron light; Small angle X-ray scattering; Synovial fluid
资金
- Danish Natural Sciences Research Council (DanScatt)
Parenteral administration of liquid crystalline phases with tunable nanostructural features and sustained release properties is a promising approach for infection treatment and local drug delivery, as well as postoperative pain management. Understanding the dynamic structural transitions of low-viscous stimulus-responsive lipid precursors in biological environments is crucial for optimizing drug delivery using this principle.
Administration of parenteral liquid crystalline phases, forming in-vivo with tunable nanostructural fea-tures and sustained release properties, offers an attractive approach for treatment of infections and local drug delivery. It has also a potential use for postoperative pain management after arthroscopic knee surgery. However, the optimal use of this drug delivery principle requires an improved understanding of the involved dynamic structural transitions after administration of low-viscous stimulus-responsive lipid precursors and their fate after direct contact with the biological environment. These precursors (preformulations) are typically based on a single biologically relevant lipid (or a lipid combination) with non lamellar liquid crystalline phase forming propensity. In relation to liquid crystalline depot design for intra-articular drug delivery, it was our interest in the present study to shed light on such dynamic structural transitions by combining synchrotron SAXS with a remote controlled addition of synovial fluid (or buffer containing 2% (w/v) albumin). This combination allowed for monitoring in real-time the hydration-triggered dynamic structural events on exposure of the lipid precursor (organic stock solution consisting of the binary lipid mixture of monoolein and castor oil) to excess synovial fluid (or excess buffer). The synchrotron SAXS findings indicate a fast generation of inverse bicontinuous cubic phases within few seconds. The effects of (i) the organic solvent N-methyl-2-pyrolidone (NMP), (ii) the lipid composition, and (iii) the albumin content on modulating the structures of the self-assembled lipid aggregates and the implications of the experimental findings in the design of liquid crystalline depots for intra-articular drug delivery are discussed. (C) 2020 Elsevier Inc. All rights reserved.
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