Lewis Oligosaccharide Vesicles for Selective BBB Drug Delivery
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Solution Overview
Problem
The challenge of delivering high molecular weight biologic agents, such as antibodies, across the blood-brain barrier (BBB) for treating brain diseases and disorders is hindered by the barrier's tight regulation, leading to indiscriminate delivery and unwanted effects in undiseased areas.
Innovation Solution
Conjugating drug delivery vehicles with Lewis A or Lewis B oligosaccharides or their mimetics to target cell adhesion molecules like E-selectin, allowing selective transport across the BBB and accumulation in active brain sites, particularly microglial cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If tagging strategies (transferrin, antibodies, glutathione) are used to increase transport across BBB, then transport of active agent into the brain is improved, but delivery becomes indiscriminate to un-diseased areas of the brain
Solution Approach 1:
The patent applies local quality by designing a targeting system that delivers drugs to specific local regions of the brain (diseased areas) rather than uniform distribution. The cell-penetrating peptide conjugate enables selective accumulation at the injection site and in target brain regions, creating localized high concentration where needed while minimizing exposure in un-diseased areas.
Solution Approach 2:
The patent uses a cell-penetrating peptide conjugate as an intermediary carrier to facilitate drug delivery across the BBB. This peptide mediator enables controlled transport of the therapeutic agent into the brain while providing targeting capability, acting as a bridge between the drug and its target site without the indiscriminate distribution problems of previous tagging strategies.
2Reliability
If high molecular weight biologic agents are used to treat brain diseases, then treatment efficacy for diseases like Alzheimer's is improved, but delivery across the BBB becomes difficult
Solution Approach 1:
The patent employs a cell-penetrating peptide conjugate as an intermediary that enables high molecular weight biologic agents to cross the BBB. This peptide mediator provides the necessary transport mechanism for large therapeutic molecules that would otherwise be unable to penetrate the blood-brain barrier, making biologics like antibodies and proteins deliverable to brain targets.
Solution Approach 2:
The patent applies parameter changes by modifying the physical-chemical properties of the therapeutic agent through conjugation with a cell-penetrating peptide. This conjugation alters the molecular characteristics of the biologic agent, enabling it to overcome the BBB barrier while retaining its therapeutic function, thus changing the delivery parameters rather than the therapeutic mechanism.
3Ease of operation
If conventional drug delivery methods are used, then simplicity of administration is maintained, but targeting precision to specific brain regions is poor
Solution Approach 1:
The patent introduces a cell-penetrating peptide conjugate as a targeting intermediary that provides spatial precision to drug delivery. This mediator enables the drug to accumulate selectively in specific brain regions through its targeting properties, achieving high measurement precision in drug localization while maintaining the simplicity of intravenous or stereotaxic injection administration.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables targeted delivery of therapeutic agents, including high molecular weight biologics, to specific brain regions, enhancing treatment efficacy for diseases like Alzheimer's disease and multiple sclerosis.
Implementation Method 1
conjugating drug delivery vehicles with Lewis A or Lewis B oligosaccharides or their mimetics to target cell adhesion molecules like E-selectin, allowing selective transport across the BBB
Data Source
AI summary
A drug delivery vehicle comprising a vesicle conjugated to one or more targeting groups, wherein the targeting groups comprise an oligosaccharide which is Lewis A or Lewis B or a mimetic thereof, or a pharmaceutically acceptable salt or PEGylated form of the oligosaccharide:wherein R represents the point of attachment to the vesicle.