Nuc1 Cell-Penetrating Peptide Ocular Drug Delivery
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Solution Overview
Problem
Current methods for delivering drugs to ocular tissues face challenges due to the eye's natural defense systems, including rapid clearance by the tear film and short half-life of drugs, making it difficult to achieve effective treatment for ocular diseases and injuries.
Innovation Solution
Development of cell-penetrating peptides (CPPs) like Nuc1, which can cross the plasma membrane without chemical conjugation, facilitating the delivery of a diverse array of agents, including proteins, antibodies, and viruses, to ocular tissues such as the retina and cornea.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional drug delivery methods are used to deliver drugs to ocular tissues, then the plasma membrane barrier prevents translocation into the cytoplasm or nucleus of cells, but this barrier function protects cells from external substances
Solution Approach 1:
The patent introduces cell-penetrating peptides (CPPs) as intermediary molecules that mediate the transport of therapeutic agents across the plasma membrane barrier. These CPPs facilitate the delivery of proteins, peptides, DNAs, siRNAs, and small molecule drugs into cells and tissues without compromising the membrane's protective function, thereby resolving the contradiction between maintaining barrier reliability and achieving effective drug delivery
2Object-affected harmful factors
If the eye's natural defense systems are present, then the tear film rapidly clears drugs from the ocular surface, but this clearance mechanism protects the eye from external contaminants
Solution Approach 1:
The patent employs cell-penetrating peptides as intermediaries that enable drugs to penetrate directly into ocular tissues, bypassing the tear film clearance mechanism. This approach allows therapeutic agents to reach their target cells without being washed away by the tear film, thus overcoming the loss of substance while maintaining the eye's natural protective defense systems
3Reliability
If drugs are delivered to the interior chamber of the eye, then therapeutic effect can be achieved, but the half-life of drugs is short due to recycling of the aqueous humor
Solution Approach 1:
The patent uses cell-penetrating peptides to deliver drugs directly into cells and tissues within the ocular interior chamber, enabling the drug to reach its target site effectively. By facilitating intracellular delivery, the therapeutic effect is enhanced while the short half-life issue is addressed through direct cellular uptake and retention mechanisms that bypass rapid aqueous humor recycling
Solution Approach 2:
The cell-penetrating peptides enable drugs to self-deliver into cells and tissues through their inherent cell-penetrating properties, allowing the therapeutic agent to accumulate at the target site and maintain effective concentrations despite the dynamic aqueous humor environment and short half-life
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
Nuc1 enhances the delivery and potency of therapeutic agents to ocular tissues, demonstrating significant penetration and efficacy in reducing apoptosis, neovascularization, fibrosis, and inflammation, while reducing the need for high doses or frequent administration.
Implementation Method 1
CPPs that enable the delivery of biologically active conjugates including proteins, peptides, DNAs, siRNAs, and small molecule drugs into cells and tissues
Data Source
AI summary
Cell penetrating peptides that target many cells types including cells of the retina and cornea with high efficiency are provided herein. These peptides can be used to deliver cargo molecules across a plasma membrane, without the need for chemical conjugation. Compositions and viral vectors comprising these cell-penetrating peptides are also provided. Methods of using the peptides, compositions and viruses to deliver various agents to target cells and tissues are also provided.