Simple-by-design approach for production of stabilizer-free cubosomes from phosphatidylglycerol and docosahexaenoic acid monoacylglycerol
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Docosahexaenoic acid monoacylglycerol represents a promising lipid constituent in the development of drug nanocarriers owing to its amphiphilicity and the beneficial health effects of this docosahexaenoic acid precursor in various disorders including cancer and inflammatory diseases. Here, we describe the formation and characterization of simple-by-design and stabilizer-free lamellar and non-lamellar crystalline nanoparticles (vesicles and cubosomes, respectively) from binary mixtures of docosahexaenoic acid monoacylglycerol and phosphatidylglycerol, which is a ubiquitous amphiphilic component present in biological systems. At the physiological temperature of 37 °C, these single amphiphilic components tend to exhibit inverse hexagonal and lamellar liquid crystalline phases, respectively, on exposure to excess water. They can also be combined and dispersed in excess water by employing a high-energy emulsification method (by means of ultrasonication) to produce through an electrostatic stabilization mechanism colloidally stable nanodispersions. A colloidal transformation from vesicles to cubosomes was detected with increasing MAG-DHA content. Through use of synchrotron small-angle X-ray scattering, cryo-transmission electron microscopy, and nanoparticle tracking analysis, we report on the structural and morphological features, and size characteristics of these nanodispersions. Depending on the lipid composition, their internal liquid crystalline architectures were spanning from a lamellar (Lα) phase to biphasic features of coexisting inverse bicontinuous (Q2) cubic Pn3m and Im3m phases. Thus, a direct colloidal vesicle-cubosome transformation was detected by augmenting the concentration of docosahexaenoic acid monoacylglycerol. The produced cubosomes were thermally stable within the investigated temperature range of 5–60 °C. Collectively, our findings contribute to understanding of the imperative steps for production of stabilizer-free cubosomes from biocompatible lipids through a simple-by-design approach. We also discuss the potential therapeutic use and future implications for development of next-generation of multifunctional vesicles and cubosomes for co-delivery of docosahexaenoic acid and drugs in treatment of diseases.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Colloid and Interface Science |
Vol/bind | 675 |
Sider (fra-til) | 825-835 |
ISSN | 0021-9797 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
Financial support to G. D. Kalaycioglu by the Scientific and Technological Research Council of Turkey (T\u00DCB\u0130TAK) B\u0130DEB-2219 International Postdoctoral Research Fellowship Program (Project No: 1059B192203132) is gratefully acknowledged. A. Yaghmur acknowledges financial supports by the Danish Council for Independent Research | Technology and Production Sciences (references DFF-7017-00065 and DFF-3105-00039B), and Novo Nordisk Foundation (Grant number NNF22OC0079752). A. Yaghmur further acknowledges financial support from the Danish Natural Sciences Research Council (DanScatt) for SAXS experiments. The authors are grateful to the beamline scientist Dr. Heinz Amenitsch (Institute of Inorganic Chemistry, Graz University of Technology) for the technical support at the Austrian SAXS beamline (ELETTRA, Trieste, Italy).
Publisher Copyright:
© 2024 The Authors
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