期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 111, 期 7, 页码 2072-2082出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2022.01.025
关键词
-
资金
- National Institutes of Health [R01 HL-70227]
This study evaluates the lamellar phase properties of lipid nanoparticles containing phosphatidylcholine and lysophosphatidylserine. The results show that lysophosphatidylserine affects the lipid packing and dynamics of the particles, and its inclusion leads to different biophysical characteristics compared to a system with double-chain phosphatidylserine. The study also finds that lysophosphatidylserine-containing nanoparticles are taken up more efficiently by immune cells in the gut, potentially influencing their oral tolerance properties.
Autoimmune conditions, allergies, and immunogenicity against therapeutic proteins are initiated by the unwanted immune response against self and non-self proteins. The development of tolerance induction approaches can offer an effective treatment modality for these clinical conditions. We recently showed that oral administration of lipidic nanoparticles containing phosphatidylcholine (PC) and lysophosphatidylserine (Lyso-PS) converted an immunogen to a tolerogen and induced immunological tolerance towards several antigens. While the biophysical properties such as lamellar characteristics of this binary lipid system are critical for stability, therapeutic delivery, and mechanism of tolerance induction, such information has not been thoroughly investigated. In the current study, we evaluated the lamellar phase properties of PC/Lyso-PS system using orthogonal biophysical methods such as fluorescence (steady-state, anisotropy, PSvue, and Laurdan), dynamic light scattering, and differential scanning calorimetry. The results showed that Lyso-PS partitioned into the PC bilayers and led to changes in the particles' lamellar phase properties, lipid-packing, and lipid-water dynamics. Additionally, the biophysical characteristics of PC/Lyso-PS system are different from the well-studied PC/double-chain phosphatidylserine (PS) system. Notably, the incorporation of LysoPS significantly reduced the hydrodynamic diameter of PC particles. Results from the in vivo uptake study and intestinal loop assay utilizing flow cytometry analysis also indicated that the uptake of Lyso-PS-containing nanoparticles by immune cells in the gut and Peyer's patches is significantly higher than that of doublechain PS due to the differential transport through microfold cells. It was also found that the acyl chain mismatch between PC and Lyso-PS is critical for the miscibility and particle stability. Collectively, the results suggest that these biophysical characteristics likely influence the in vivo behaviors and contribute to the oral tolerance property of PC/Lyso-PS system. (C) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
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