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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
CNS delivery via adsorptive transcytosis
Françoise Hervé1, Nicolae Ghinea, Jean-Michel Scherrmann
1UFR Biomédicale, Université Paris Descartes, CNRS, UPR2228, 45 rue des Saints-Pères, 75270 Paris, France. francoise.herve@univ-paris5.fr
The AAPS Journal
|August 30, 2008
Summary
Adsorptive-mediated transcytosis (AMT) facilitates brain drug delivery across the blood-brain barrier (BBB). This review explores cationized proteins and cell-penetrating peptides (CPPs) for enhanced neurotherapeutics, highlighting mechanisms and limitations.
Area of Science:
- Neuroscience
- Pharmacology
- Biotechnology
Background:
- The blood-brain barrier (BBB) presents a significant challenge for delivering therapeutics to the brain.
- Adsorptive-mediated transcytosis (AMT) is a natural process utilized by the BBB for molecular transport.
- Understanding BBB transport mechanisms is crucial for developing effective neurotherapeutics.
Purpose of the Study:
- To review the mechanisms of adsorptive-mediated transcytosis (AMT) across the blood-brain barrier (BBB).
- To discuss the application of cationized proteins and cell-penetrating peptides (CPPs) for brain drug delivery.
- To highlight the potential and limitations of AMT-based strategies for neurotherapeutics.
Main Methods:
- Review of existing literature on adsorptive-mediated transcytosis (AMT) at the BBB.
- Discussion of protein cationization techniques using polyamines.
- Analysis of cell-penetrating peptide (CPP) strategies, including Tat-derived peptides and Syn-B vectors.
Main Results:
- AMT leverages the BBB's endothelial cell surface for binding, uptake, and exocytosis of cationic molecules.
- Cationized proteins and CPPs have demonstrated potential for delivering various molecules across the BBB.
- Limitations include toxicity, immunogenicity, and instability of peptide vectors.
Conclusions:
- AMT offers a viable pathway for brain drug delivery, utilizing the BBB's inherent transport capabilities.
- Cationized proteins and CPPs represent promising vectors for neurotherapeutics, but require further optimization.
- Enhanced understanding of AMT mechanisms is essential for advancing brain-targeted drug delivery.
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