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New Drug Delivery Systems Developed for Brain Targeting

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Abstract

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSF) are two of the most complex and sophisticated concierges that defend the central nervous system (CNS) by numerous mechanisms. While they maintain the neuro-ecological homeostasis through the regulated entry of essential biomolecules, their conservative nature challenges the entry of most of the drugs intended for CNS delivery. Targeted delivery challenges for a diverse spectrum of therapeutic agents/drugs (non-small molecules, small molecules, gene-based therapeutics, protein and peptides, antibodies) are diverse and demand specialized delivery and disease-targeting strategies. This review aims to capture the trends that have shaped the current brain targeting research scenario. This review discusses the physiological, neuropharmacological, and etiological factors that participate in the transportation of various drug delivery cargoes across the BBB/BCSF and influence their therapeutic intracranial concentrations. Recent research works spanning various invasive, minimally invasive, and non-invasive brain- targeting approaches are discussed. While the pre-clinical outcomes from many of these approaches seem promising, further research is warranted to overcome the translational glitches that prevent their clinical use. Non-invasive approaches like intranasal administration, P-glycoprotein (P-gp) inhibition, pro-drugs, and carrier/targeted nanocarrier-aided delivery systems (alone or often in combination) hold positive clinical prospects for brain targeting if explored further in the right direction.

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Authors and Affiliations

  1. Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad, Gujarat, 382481, India

    Shruti U. Rawal & Mayur M. Patel

  2. Department of Pharmacology, Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad, Gujarat, 382481, India

    Bhoomika M. Patel

  3. Department of Pharmaceutical Technology, L.J. Institute of Pharmacy, L J University, Sarkhej-Sanand Circle Off. S.G. Road, Ahmedabad, Gujarat, 382210, India

    Shruti U. Rawal

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  1. Shruti U. Rawal
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  2. Bhoomika M. Patel
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  3. Mayur M. Patel
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Mayur Patel, Shruti Rawal and Bhoomika Patel declare no conflicts of interest.

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RS: Writing the original draft, data curation, visualization, editing, and revision, PB, and PM: Writing, visualization, editing, and supervision. All the authors have read and approved the final version of the manuscript and agree to be accountable for the work.

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Rawal, S.U., Patel, B.M. & Patel, M.M. New Drug Delivery Systems Developed for Brain Targeting. Drugs 82, 749–792 (2022). https://doi.org/10.1007/s40265-022-01717-z

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