Serena Omo-Lamai, Jia Nong, Krupa Savalia, Brian J. Kelley, Jichuan Wu, Sahily Esteves-Reyes, Liam S. Chase, Vladimir R. Muzykantov, Oscar A. Marcos-Contreras, Jean-Pierre Dollé, Douglas H. Smith, Jacob S. Brenner.
Abstract
Traumatic brain injury has faced numerous challenges in drug development, primarily due to the difficulty of effectively delivering drugs to the brain. However, there is a potential solution in targeted drug delivery methods involving antibody-drug conjugates or nanocarriers conjugated with targeting antibodies. Following a TBI, the blood-brain barrier (BBB) becomes permeable, which can last for years and allow the leakage of harmful plasma proteins.
Introduction
Traumatic brain injury (TBI) results in 230,000 hospitalizations and 50,000 deaths in the US each year annually. While there have been multiple TBI clinical treatment trials, to-date none have been successful. One major challenge is that most candidate drugs have poor accumulation in the brain, due to exclusion by the blood-brain barrier (BBB). One potential solution to this problem is to develop targeted drug delivery vehicles that can localize drugs to the injured brain.
Materials and Methods:
Liposomes were formulated using the thin-film hydration method. Lipids were dissolved in chloroform and combined in a borosilicate glass tube. Chloroform was evaporated by blowing nitrogen over the solution until visibly dry (approximately15 minutes) then putting the tube under vacuum for greater than 1 hour. Dried lipid films were hydrated with phosphate buffered saline to a total lipid concentration of 20mM.
Discussion:
In this study, we found that antibodies and nanocarriers targeted to brain endothelial epitopes accumulate in the brain at higher levels than untargeted IgG controls. In the most powerful example of this, VCAM-1-targeted liposomes achieved more than 10-fold higher delivery to the brain than untargeted IgG-conjugated nanocarriers.
Acknowledgments:
We thank Muzykantov and Brenner lab members for their technical and mental support. We also thank Hui Wei for her help with imaging.
Citation: Omo-Lamai S, Nong J, Savalia K, Kelley BJ, Wu J, Esteves-Reyes S, et al. (2024) Targeting of nanoparticles to the cerebral vasculature after traumatic brain injury. PLoS ONE 19(6): e0297451. https://doi.org/10.1371/journal.pone.0297451
Editor: Kazuhiko Kibayashi, School of Medicine, Tokyo Women’s Medical University, JAPAN
Received: June 14, 2023; Accepted: January 4, 2024; Published: June 10, 2024.
Copyright: © 2024 Omo-Lamai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: S.O. received funding from the American Heart Association (Grant 23PRE1014444). J.N. received funding from the American Heart Association (Grant 916172). B.J.K received funding from National Health Institute (K08-NS110929). O.A.M.-C. received funding from the American Heart Association (Grant 19CDA34590001). J.S.B. and V.M.R. received support from the Cardiovascular Institute of the University of Pennsylvania. V.M.R. received funding from National Institute of Health (R01 HL155106, R01 HL128398, R01 HL143806). J.S.B. received funding from National Institute of Health (K08-HL-138269, R01-HL-153510, R01-HL-160694, R01-HL-157189, R21-AI-166778-01). D.H.S received funding from the Paul G. Allen Family Foundation and National Institute of Health (U54 NS115322). AHA: https://www.heart.org/en/get-involved/ways-to-give?form=FUNPHPZDXBX&s_src=23L511AEMG&s_subsrc=fy23_jun_sem_google_text_&utm_medium=paid&utm_campaign=dr+fy23+june&utm_source=sem+google&utm_content=prospecting-remarketing+sem+general&utm_term=text&gad=1&gclid=CjwKCAjwp6CkBhB_EiwAlQVyxUMZ_FbtTs7VO9Lig6RdFLrTCBLy_fDCRjQoyJToLTNRKw3B3axoQhoC4ZwQAvD_BwE&gclsrc=aw.ds CVI: https://www.med.upenn.edu/cvi/funded-dream-teams.html NIH: https://www.nih.gov/grants-funding The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
