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Systemic delivery to central nervous system by engineered PLGA nanoparticles.

Qiang Cai1, Long Wang1, Gang Deng1

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Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) show promise for delivering drugs across the blood-brain barrier (BBB) to treat neurological disorders. Engineering these PLGA NPs with pre-transcytosis, transcytosis, and post-transcytosis strategies is key for clinical success.

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Neuroscience

Background:

  • Neurological disorders pose a significant global health challenge.
  • Current pharmaceutical treatments are limited by the blood-brain barrier (BBB) restricting central nervous system drug access.
  • Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are a promising strategy for overcoming BBB drug delivery limitations.

Purpose of the Study:

  • To classify and review strategies for engineering PLGA NPs to cross the BBB.
  • To categorize PLGA NP adaptations into pre-transcytosis, transcytosis, and post-transcytosis strategies.
  • To highlight the necessity of combining these strategies for effective clinical translation.

Main Methods:

  • Classification of PLGA NP modifications into three generations based on their function.
  • Review of strategies aimed at facilitating NP travel from injection sites (pre-transcytosis).
  • Analysis of methods to enhance NP passage across brain endothelial cells (BBB transcytosis).
  • Examination of techniques for targeting impaired nervous system cells (post-transcytosis).

Main Results:

  • PLGA NPs can be engineered using distinct strategies to improve BBB penetration.
  • First-generation NPs focus on pre-transcytosis, second on BBB transcytosis, and third on post-transcytosis.
  • Each generation addresses specific challenges in drug delivery across the BBB.

Conclusions:

  • Multifunctional PLGA NPs integrating pre-transcytosis, BBB transcytosis, and post-transcytosis strategies are essential.
  • Combining these strategies is crucial for achieving successful translational applications in treating neurological disorders.
  • Further engineering of PLGA NPs is required to overcome existing limitations for clinical use.