Blood-brain barrier penetrant therapeutic delivery with biomacromolecule-tagged constructs

This technology uses nanoscale constructs tagged with biomacromolecules like peptides, nucleic acids, and carbohydrates to deliver therapeutic agents across the blood-brain barrier, enhancing drug delivery to the brain while minimizing off-target effects.

Background

The blood-brain barrier (BBB) is a critical physiological structure that serves to protect the brain from harmful substances in the bloodstream while maintaining the necessary environment for neural function. This barrier is composed of tightly packed endothelial cells that restrict the passage of most molecules, making it a significant challenge for drug delivery to the brain. The need for effective delivery systems is particularly pressing in the treatment of neurological disorders and brain cancers, where therapeutic agents must reach the brain in sufficient concentrations to be effective.

Traditional methods to bypass the BBB, such as intracranial injections or osmotic disruption, are invasive and carry risks of damage and infection. As a result, there is a growing interest in developing less invasive methods that can safely and effectively deliver drugs across the BBB.

Alternative methods that utilize natural transport mechanisms, such as receptor-mediated transcytosis, often struggle with issues like rapid degradation of therapeutic agents and short circulation times. Peptide-based delivery systems, while promising, suffer from enzymatic degradation and off-target effects. Nucleic acids, although capable of high specificity through aptamer technology, are prone to rapid clearance and degradation. Carbohydrate-based systems, leveraging glucose transporters, face challenges in achieving selective targeting due to the ubiquitous nature of glucose receptors throughout the body. These limitations highlight the need for innovative solutions that can overcome the inherent challenges of drug delivery to the brain.

Technology description

This technology involves the creation of nanoscale constructs that are tagged with biomacromolecules to enhance the delivery of therapeutic agents across the blood-brain barrier (BBB). The constructs employ peptides, nucleic acids, and carbohydrates as targeting ligands to utilize natural transport mechanisms of the BBB, such as receptor-mediated transcytosis.

Peptides are conjugated to nanoscale materials like liposomes or polymeric nanoparticles to improve stability and circulation time, targeting receptors like the transferrin receptor. Nucleic acids, particularly DNA and RNA aptamers, are selected through SELEX technology for specific BBB receptors, with challenges like rapid degradation mitigated by nanoparticle conjugation. Carbohydrates, such as glucose, target glucose transporters on the BBB, leveraging the brain's high glucose demand for selective delivery. These nanoscale systems aim to enhance drug delivery to the brain while reducing off-target effects, providing a less invasive alternative to traditional methods.

The differentiation of this technology lies in its innovative approach to overcoming the BBB's impermeability, which has been a significant challenge in drug delivery to the brain. Traditional methods often involve invasive techniques, whereas this technology leverages naturally occurring active transport mechanisms on the BBB, making it less invasive and more biocompatible.

By using biomacromolecules as targeting ligands, the technology ensures selective and efficient delivery of therapeutic agents. The use of nanoscale constructs allows for the conjugation of multiple functional moieties, enhancing targeting specificity and therapeutic efficacy. The incorporation of peptides, nucleic acids, and carbohydrates provides a versatile platform that can be tailored for various therapeutic applications, including cancer treatment and neurodegenerative diseases, setting it apart from other drug delivery systems.

Benefits

Facilitates delivery of therapeutic agents across the blood-brain barrier (BBB)
Utilizes biomacromolecules like peptides, nucleic acids, and carbohydrates as targeting ligands
Exploits natural transport mechanisms such as receptor-mediated transcytosis
Enhances stability and circulation time of therapeutic agents
Minimizes off-target effects and offers a less invasive alternative to traditional methods
Improves drug delivery to the brain, potentially aiding in the treatment of brain diseases and cancers
Allows for multifunctional targeting using nanoscale constructs