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Targeted and transient opening of the blood brain barrier in discrete neurocircuits and brain regions

Neuropsychopharmacology volume 48, pages 253–254 (2023)Cite this article

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Delivery of macromolecular therapeutics to the brain faces numerous obstacles, chief of which is transporting them across the blood brain barrier (BBB) of the central nervous system (CNS), in part due to the tight junctions between endothelial cells of the neurovasculature. Despite these difficulties, neuropeptide systems have been continuously noted as promising therapeutic targets. Neuropeptides are often released and diffuse slower than neurotransmitters, and their binding at g-protein coupled receptors have long-lasting effects, making them ideal therapeutic candidates [1, 2]. Yet, the full clinical potential of most neuropeptides remains unrealized as they do not readily translocate across the BBB. Other peptide systems, such as μ-opioid receptor targeting drugs, present the opposite obstacle—they readily diffuse across the BBB, but their ubiquitous actions throughout the brain and periphery lead to off-target issues. Imaging-guided delivery technologies can address these limitations by shuttling therapeutic peptides across the BBB and into specific brain regions, thereby enabling direct access to their therapeutic neuronal target without off-target biodistribution.

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Fig. 1: Representative model for how focused ultrasound can be combined with nanoemulsions for precision drug delivery to the brain.

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Acknowledgements

We thank members of the Crowley and Medina labs for helpful discussions related to this topic.

Funding

NAC is supported by NIH grants R01AA029403-01A1, R21AA028088-01, and P50AA017823. SHM is supported by NIH grants R21DK128638-01A1, R35GM142902-01, and NSF grant DMR-1845053. NAC and SHM are jointly supported by the Benkovic Research Initiative

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Authors and Affiliations

  1. Department of Biology, Penn State University, University Park, PA, 16802, USA

    Nicole A. Crowley

  2. Department of Biomedical Engineering, Penn State University, University Park, PA, 16802, USA

    Nicole A. Crowley & Scott H. Medina

  3. The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA

    Nicole A. Crowley & Scott H. Medina

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  1. Nicole A. Crowley
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  2. Scott H. Medina
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NAC and SHM jointly conceived the topic for this commentary based on shared funding. NAC and SEM contributed equally to manuscript preparation.

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Correspondence to Nicole A. Crowley or Scott H. Medina.

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Crowley, N.A., Medina, S.H. Targeted and transient opening of the blood brain barrier in discrete neurocircuits and brain regions. Neuropsychopharmacol. 48, 253–254 (2023). https://doi.org/10.1038/s41386-022-01380-8

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  • DOI: https://doi.org/10.1038/s41386-022-01380-8

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