title: Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier.
abstract: The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: David S
authors.initials: DS
authors.lastname: Hersh
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Aniket S
authors.initials: AS
authors.lastname: Wadajkar
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Nathan
authors.initials: N
authors.lastname: Roberts
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Jimena G
authors.initials: JG
authors.lastname: Perez
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Nina P
authors.initials: NP
authors.lastname: Connolly
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Victor
authors.initials: V
authors.lastname: Frenkel
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Winkles
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Woodworth
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).|Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (USA).|Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201 (USA).
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001927:Brain Diseases / Q000188:drug therapy*; D002491:Central Nervous System Agents / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans
chemical_list: D002491:Central Nervous System Agents