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1. Biodegradable polyanhydride-based nanomedicines for blood to brain drug delivery: Nanomedicines for blood to brain drug delivery

   https://doi.org/10.1002/jbm.a.36477  

   Brenza, Timothy M. ; Schlichtmann, Benjamin W. ; Bhargavan, Biju ; Vela Ramirez, Julia E. ; Nelson, Rainie D. ; Panthani, Matthew G. ; McMillan, JoEllyn M. ; Kalyanaraman, Balaraman ; Gendelman, Howard E. ; Anantharam, Vellareddy ; et al ( October 2018 , Journal of Biomedical Materials Research Part A)
2. Drug Delivery to the Brain across the Blood–Brain Barrier Using Nanomaterials

   https://doi.org/10.1002/smll.201701921  

   Tsou, Yung‐Hao ; Zhang, Xue‐Qing ; Zhu, He ; Syed, Sahla ; Xu, Xiaoyang ( October 2017 , Small)

   A major obstacle facing brain diseases such as Alzheimer's disease, multiple sclerosis, brain tumors, and strokes is the blood–brain barrier (BBB). The BBB prevents the passage of certain molecules and pathogens from the circulatory system into the brain. Therefore, it is nearly impossible for therapeutic drugs to target the diseased cells without the assistance of carriers. Nanotechnology is an area of growing public interest; nanocarriers, such as polymer‐based, lipid‐based, and inorganic‐based nanoparticles can be engineered in different sizes, shapes, and surface charges, and they can be modified with functional groups to enhance their penetration and targeting capabilities. Hence, understanding the interaction between nanomaterials and the BBB is crucial. In this Review, the components and properties of the BBB are revisited and the types of nanocarriers that are most commonly used for brain drug delivery are discussed. The properties of the nanocarriers and the factors that affect drug delivery across the BBB are elaborated upon in this review. Additionally, the most recent developments of nanoformulations and nonconventional drug delivery strategies are highlighted. Finally, challenges and considerations for the development of brain targeting nanomedicines are discussed. The overall objective is to broaden the understanding of the design and to develop nanomedicines for the treatment of brain diseases.

    

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3. Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate Traumatic Brain Injury

   https://doi.org/10.3390/pharmaceutics16060774  

   Yanamadala, Yaswanthi ; Roy, Ritika ; Williams, Afrika Alake ; Uppu, Navya ; Kim, Audrey Yoonsun ; DeCoster, Mark A ; Kim, Paul ; Murray, Teresa Ann ( June 2024 , Pharmaceutics)

   Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood–brain barrier (BBB), which prevents the passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal (IN) administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of proinflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance after TBI in KAFAK-treated mice. This study demonstrates KAFAK’s ability to cross the blood–brain barrier, to lower proinflammatory cytokines in vivo, and to restore function after a moderate TBI.

    

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4. Delivery of Nanoparticles and Macromolecules across the Blood–Brain Barrier

   https://doi.org/10.1002/adtp.201900073  

   Nowak, Maksymilian ; Helgeson, Matthew E. ; Mitragotri, Samir ( September 2019 , Advanced Therapeutics)

   Treatment of brain‐related diseases is challenging due to the presence of the blood–brain barrier (BBB), a hurdle that prevents most foreign matter from entering the brain. While macromolecules and nanoparticles represent an increasing fraction of the therapeutic landscape in general, their limited ability to cross the BBB has hindered their clinical impact in treating diseases of the central nervous system. Here, the various routes for entry of macromolecular therapeutics into the brain are discussed, as well as the methods used to enhance their transport. Particular emphasis is placed on highlighting quantitative trends and mechanistic insights into how the macromolecular transport can be improved, discussing novel enhancement strategies, and identifying areas in need of more detailed investigations. Overall, this review shows several promising advances and continued progress toward a more complete understanding of how macromolecule and nanoparticle design and delivery strategy characteristics can be leveraged to improve the treatment of brain diseases.

    

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5. Birth delivery mode alters perinatal cell death in the mouse brain

   https://doi.org/10.1073/pnas.1811962115  

   Castillo-Ruiz, Alexandra ; Mosley, Morgan ; Jacobs, Andrew J. ; Hoffiz, Yarely C. ; Forger, Nancy G. ( October 2018 , Proceedings of the National Academy of Sciences)