Blood-Brain Barrier Shuttle Peptide Development for Stroke

Brain delivery is one of the major challenges in stroke drug development due to the presence of the blood-brain barrier (BBB). However, the blood-brain barrier can protect the brain and allow nutrients to enter through a variety of mechanisms. These mechanisms provide an attractive avenue for the treatment of stroke. Peptide shuttles can utilize these mechanisms to increase the transport of compounds that cannot cross the BBB independently. In recent years, peptide shuttle proteins have received increasing attention due to their lower cost, lower immunogenicity, and greater chemical versatility than traditional antibodies and other proteins.

Fig. 1. A new therapeutic strategy for ischemic stroke is shuttle peptides that ensure drug permeability across the BBB.Fig. 1. Sources of BBB-shuttle peptides. (Oller-Salvia et al., 2016)

Our Blood-Brain Barrier Shuttle Peptide Development Services

Ace Therapeutics provides comprehensive BBB-shuttle peptide development services. Our team of expert peptide chemists and bioengineers apply our extensive knowledge of peptide structure-activity relationships to find BBB-shuttle peptides that enhance the translocation of stroke drugs.

Types of BBB-Shuttle Peptides We Can Develop

  • BBB-shuttle peptides derived from natural sources.
  • BBB-shuttle peptides discovered by phage display: This involves screening against phage libraries of targets of interest, in which each phage is genetically modified to display a specific peptide or protein on its coat protein.
  • Discovery of novel protease-resistant BBB-shuttle peptides: DNA or mRNA encoding libraries from chemistry library.

Design of BBB-Shuttle Peptides

  • We offer several strategies for designing BBB-Shuttle peptides that exhibit increased stability to serum proteases, including using D-amino acids to construct a given peptide and reversing the order of the sequence.
  • We use a variety of computational methods to predict the BBB permeability of peptides, including cheminformatics filters, molecular dynamics simulations, statistical models, and/or artificial intelligence algorithms.

Preclinical Evaluation of BBB-Shuttle Peptides

We offer comprehensive preclinical evaluation services to help clients analyze the ability of BBB-Shuttle peptides to transport stroke drugs across the BBB and into the brain parenchyma, which is critical for the development of effective CNS-targeted therapies.

  • Passive diffusion BBB models: Provide information on the permeability and transport kinetics of BBB-shuttle peptides.
  • Cellular uptake: Investigate the cellular uptake and endocytosis of BBB-shuttle peptides in relevant cell types (e.g., brain endothelial cells) to help clients understand the mechanisms and efficacy of peptide-based drug delivery systems into cells.
  • Cell-based BBB models: Incorporate co-cultures of multiple cell types (brain endothelial cells, pericytes, astrocytes, and neurons) to provide more physiologically relevant assessments of BBB permeability and transport.
  • In vivo intracerebral microdialysis: Direct measurement of the concentration of BBB-shuttle peptides or related drugs in brain interstitial fluid allows real-time monitoring of brain permeation and pharmacokinetics.
  • In vivo non-invasive imaging: Positron emission tomography (PET) or magnetic resonance imaging (MRI) to visualize and quantify the distribution of BBB-shuttle peptides in the brain.
  • In vivo two-photon microscopy: High-resolution, real-time visualization of BBB peptide distribution and interactions with brain vasculature and parenchyma.
  • In vitro quantification of whole organs: Involve the collection and analysis of whole organs (e.g., the brain) to quantify the amount of BBB-shuttle peptide that has accumulated.
  • In vitro quantification of organ homogenates: Harvested organs are homogenized and analyzed to quantify peptide levels. This allows for a more detailed assessment of regional distribution within the brain.
  • Ex vivo microscopy: Use microscopy techniques, such as fluorescence microscopy or electron microscopy, to visualize the localization and interactions of BBB-shuttle peptides within brain tissue. Provide high-resolution information on the cellular and subcellular distribution of the peptide.

Ace Therapeutics is your trusted partner, provides comprehensive services for the development of BBB-shuttle peptides for the treatment of stroke. If you are interested in our services, please do not hesitate to contact us!

Reference
  1. Oller-Salvia, B., et al. (2016). Blood–brain barrier shuttle peptides: an emerging paradigm for brain delivery. Chemical Society Reviews, 45(17), 4690-4707.
All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
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