PreprintArticleVersion 1This version is not peer-reviewed
Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice
Version 1
: Received: 29 July 2024 / Approved: 29 July 2024 / Online: 30 July 2024 (07:35:59 CEST)
How to cite:
Lee, J.; De La Torre, A. L.; Rawlinson, F. L.; Ness, D. B.; Lewis, L. D.; Hickey, W. F.; Chang, C. C.; Chang, T. Y. Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice. Preprints2024, 2024072417. https://doi.org/10.20944/preprints202407.2417.v1
Lee, J.; De La Torre, A. L.; Rawlinson, F. L.; Ness, D. B.; Lewis, L. D.; Hickey, W. F.; Chang, C. C.; Chang, T. Y. Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice. Preprints 2024, 2024072417. https://doi.org/10.20944/preprints202407.2417.v1
Lee, J.; De La Torre, A. L.; Rawlinson, F. L.; Ness, D. B.; Lewis, L. D.; Hickey, W. F.; Chang, C. C.; Chang, T. Y. Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice. Preprints2024, 2024072417. https://doi.org/10.20944/preprints202407.2417.v1
APA Style
Lee, J., De La Torre, A. L., Rawlinson, F. L., Ness, D. B., Lewis, L. D., Hickey, W. F., Chang, C. C., & Chang, T. Y. (2024). Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice. Preprints. https://doi.org/10.20944/preprints202407.2417.v1
Chicago/Turabian Style
Lee, J., Catherine C.Y. Chang and Ta Yuan Chang. 2024 "Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice" Preprints. https://doi.org/10.20944/preprints202407.2417.v1
Abstract
Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
