Transdermal Delivery Modulating Epithelial Junctions

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Solution Overview

Problem

Current methods for transdermal drug delivery are limited by the skin's barrier properties, particularly the stratum corneum, and are ineffective for high molecular weight agents like peptides, proteins, and nucleic acids, often relying on harsh solvents and patch-based systems that restrict molecular size, lipophilicity, and potency.

Innovation Solution

The use of transdermal delivery formulations that include junctional protein modulators such as Clostridium perfringens enterotoxin, zona occludens toxin, chitosan, and acto-myosin belt modulators to penetrate the skin, modulating tight junctions and acto-myosin belts to enhance the absorption of a wide range of active agents, including those for cancer, kidney disease, and skin conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If harsh solvents or patch-based systems are used to enhance transdermal penetration, then penetration of the stratum corneum is improved, but the molecular size, lipophilicity, and potency of drugs are restricted and toxicity increases

Engineering Contradiction:
Improvetransdermal penetration efficiencyVSAvoidmolecular size range
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses Chemical Permeation Enhancers (CPEs) as intermediary substances that temporarily interact with the stratum corneum to increase its permeability. These CPEs act as mediators between the drug and the skin barrier, allowing various molecular sizes and types to penetrate without requiring harsh solvents or patch-based systems. The CPEs modify the skin barrier properties temporarily, enabling broader drug versatility while maintaining safety.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If Chemical Permeation Enhancers are used to increase skin permeability, then transdermal absorption is improved, but skin damage, irritation and sensitization occur

Engineering Contradiction:
Improvetransdermal absorption rateVSAvoidskin irritation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs CPEs that temporarily alter the physical and chemical parameters of the stratum corneum, such as increasing hydration levels and modifying lipid organization. These parameter changes are reversible and controlled, allowing enhanced permeability without causing permanent skin damage, irritation, or sensitization. The changes are optimized to achieve adequate penetration while maintaining skin integrity.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If the stratum corneum barrier is maintained intact, then skin protection is preserved, but transdermal delivery of high molecular weight agents is ineffective

Engineering Contradiction:
Improveskin barrier functionVSAvoiddelivery of high molecular weight agents
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies CPEs before administering high molecular weight agents to preliminarily enhance the skin permeability. This preliminary action temporarily modifies the stratum corneum properties, creating favorable conditions for the subsequent delivery of high molecular weight agents. After delivery, the skin barrier naturally recovers, maintaining long-term protection while enabling effective transdermal drug delivery during the treatment period.

Inventive Principle:
Principle #10Preliminary action

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

This approach allows for improved penetration and absorption of larger molecules across the skin, overcoming the stratum corneum and deeper skin layers without harsh solvents, enabling effective delivery of high molecular weight agents and enhancing skin permeability with reduced toxicity.

Implementation Method 1

modulating tight junctions and acto-myosin belts to enhance the absorption of a wide range of active agents

Methodology Applied
Scientific EffectTight junction modulation:

Implementation Method 2

increase its permeability

Methodology Applied
Scientific EffectPermeation enhancement: Permeation

Data Source

PatentUS20220323344A1Transdermal penetration by modulating epithelial junctions
Publication Date: 2022.10.13 DYVE BIOSCIENCES INC

AI summary

Embodiments include a transdermal delivery formulation and method for transdermal delivery of an active agent for systemic distribution. A formulation can be applied to skin, nail or hair follicle of a subject. After penetrating the stratum corneum, the agent can pass through other layers of skin as junctional proteins and/or acto-myosin belts between cells are modulated. The formulation can include one or more agents to treat a disease, ailment or an anesthetic to alleviate pain. Alternatively, it can include one or more nutrients, vitamins, minerals or supplements to promote health and well-being.