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The Blood-brain Barrier00:49

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Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
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Body:After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt...
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Chemically Designed Functional Nanomicelles for Blood-Brain Barrier Crossing.

Ankan Kumar Sarkar1, Sudipta Jana2, Guneet Kaur3

  • 1School of Materials Science, Indian Association for the Cultivation of Science, Kolkata 700032, West Bengal, India.

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Optimized polymer nanomicelles efficiently cross the blood-brain barrier (BBB) via receptor-mediated or adsorption-mediated transcytosis. This breakthrough enhances brain drug delivery, potentially revolutionizing treatments for neurological disorders.

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Neuroscience

Background:

  • The blood-brain barrier (BBB) presents a significant obstacle for drug delivery to the central nervous system.
  • Current nanocarrier strategies for crossing the BBB via receptor-mediated transcytosis (RMT) or adsorption-mediated transcytosis (AMT) have limited efficiency.

Purpose of the Study:

  • To develop and evaluate novel polymer nanomicelles capable of efficient BBB penetration.
  • To elucidate the critical factors governing RMT and AMT for nanocarrier design.

Main Methods:

  • Fabrication of 20-60 nm polymer nanomicelles.
  • Assessment of BBB crossing in transwell models, tumor spheroids, and in vivo mouse models.
  • Analysis of nanocarrier properties influencing RMT and AMT.

Main Results:

  • Optimized nanomicelles demonstrated significantly enhanced BBB transcytosis (8-10 times).
  • Lower receptor density was found critical for RMT, while membrane penetration was key for AMT.
  • Achieved 8-fold enhanced penetration in tumor spheroids and 26-35 times greater delivery to deep brain tissues.

Conclusions:

  • Developed polymer nanomicelles show high potential for efficient BBB transport.
  • Tailoring nanocarrier properties can optimize RMT and AMT pathways for enhanced brain delivery.
  • These nanomicelles represent promising carriers for in vivo delivery of therapeutic biomolecules to the brain.