Lipid Nanosystems and Serum Protein as Biomimetic Interfaces: Predicting the Biodistribution of a Caffeic Acid-Based Antioxidant

Autor: Fernandes E, Benfeito S, Cagide F, Gonçalves H, Bernstorff S, Nieder JB, CD Real Oliveira ME, Borges F, Lúcio M
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nanotechnology, Science and Applications, Vol Volume 14, Pp 7-27 (2021)
Druh dokumentu: article
ISSN: 1177-8903
95315381
Popis: Eduarda Fernandes,1,2 Sofia Benfeito,3 Fernando Cagide,3 Hugo Gonçalves,4 Sigrid Bernstorff,5 Jana B Nieder,2 M Elisabete CD Real Oliveira,1 Fernanda Borges,3 Marlene Lúcio1,6 1Departamento de Física da Universidade do Minho, CF-UM-UP, Centro de Física das Universidades do Minho e Porto, Campus de Gualtar, Braga, 4710-057, Portugal; 2 Ultrafast Bio- and Nanophotonics Group, INL – International Iberian Nanotechnology Laboratory, Braga, Portugal; 3CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal; 4Paralab, SA, Valbom, 4420-392, Portugal; 5Elettra-Sincrotrone Trieste S. C.p.A.,, Basovizza, Trieste, I-34149, Italy; 6CBMA, Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, Campus de Gualtar, Braga 4710-057, PortugalCorrespondence: Marlene LúcioUniversidade do Minho, Campus de Gualtar, Braga 4710-057, PortugalEmail mlucio@fisica.uminho.ptFernanda BorgesCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, PortugalEmail fborges@fc.up.ptPurpose: AntiOxCIN3 is a novel mitochondriotropic antioxidant developed to minimize the effects of oxidative stress on neurodegenerative diseases. Prior to an investment in pre-clinical in vivo studies, it is important to apply in silico and biophysical cell-free in vitro studies to predict AntiOxCIN3 biodistribution profile, respecting the need to preserve animal health in accordance with the EU principles (Directive 2010/63/EU). Accordingly, we propose an innovative toolbox of biophysical studies and mimetic models of biological interfaces, such as nanosystems with different compositions mimicking distinct membrane barriers and human serum albumin (HSA).Methods: Intestinal and cell membrane permeation of AntiOxCIN3 was predicted using derivative spectrophotometry. AntiOxCIN3 –HSA binding was evaluated by intrinsic fluorescence quenching, synchronous fluorescence, and dynamic/electrophoretic light scattering. Steady-state and time-resolved fluorescence quenching was used to predict AntiOxCIN3-membrane orientation. Fluorescence anisotropy, synchrotron small- and wide-angle X-ray scattering were used to predict lipid membrane biophysical impairment caused by AntiOxCIN3 distribution.Results and Discussion: We found that AntiOxCIN3 has the potential to permeate the gastrointestinal tract. However, its biodistribution and elimination from the body might be affected by its affinity to HSA (> 90%) and by its steady-state volume of distribution (VDSS=1.89± 0.48 L∙Kg− 1). AntiOxCIN3 is expected to locate parallel to the membrane phospholipids, causing a bilayer stiffness effect. AntiOxCIN3 is also predicted to permeate through blood-brain barrier and reach its therapeutic target – the brain.Conclusion: Drug interactions with biological interfaces may be evaluated using membrane model systems and serum proteins. This knowledge is important for the characterization of drug partitioning, positioning and orientation of drugs in membranes, their effect on membrane biophysical properties and the study of serum protein binding. The analysis of these interactions makes it possible to collect valuable knowledge on the transport, distribution, accumulation and, eventually, therapeutic impact of drugs which may aid the drug development process.Keywords: biomimetic models, biophysical profiling, drug–membrane interaction, blood–brain barrier permeability, drug distribution, small and wide-angle X-ray diffraction
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