Transdermal NO Formulation for Sustained Systemic Delivery
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Solution Overview
Problem
Existing delivery methods for therapeutic agents face bioavailability issues due to low solubility, poor uptake, and rapid elimination, limiting effective systemic or local delivery to targeted sites, particularly for nitric oxide (NO) which is crucial for preventing and treating endothelial dysfunction.
Innovation Solution
A transdermal formulation comprising an NO booster and/or precursor, solvent, and optionally a fatty acid, which enhances systemic NO levels and reduces ROS production, delivered through the skin to bypass gastrointestinal tract and achieve sustained therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If oral or IV routes of administration are used to deliver therapeutic agents, then systemic delivery is achieved, but inadequate therapeutic levels are reached at the targeted local site due to bioavailability issues
Solution Approach 1:
The patent employs a transdermal delivery system as an intermediary route between oral/IV administration and direct local delivery. This mediator bypasses the gastrointestinal tract and first-pass liver metabolism, allowing therapeutic agents to enter systemic circulation through the skin while achieving adequate local concentrations at target sites without the bioavailability limitations of traditional routes
Solution Approach 2:
The invention segments the delivery process into distinct phases: (1) transdermal penetration through the skin barrier, (2) controlled release into systemic circulation, and (3) targeted delivery to specific tissues. This segmentation allows optimization of each phase independently, overcoming the limitations of conventional single-route administration
2Quantity of substance
If therapeutic agents are delivered systemically to achieve adequate levels, then bioavailability is improved, but rapid elimination by the liver (first pass limitations) prevents sustained therapeutic effect
Solution Approach 1:
The transdermal delivery system performs preliminary action by pre-loading the therapeutic agent into the skin matrix before systemic absorption occurs. This creates a reservoir that gradually releases the agent into circulation, preventing rapid hepatic elimination and maintaining sustained therapeutic levels without requiring continuous high-dose administration
Solution Approach 2:
The invention establishes continuity of useful action through controlled sustained release from the transdermal reservoir. The therapeutic agent is continuously delivered into systemic circulation at optimized rates, maintaining constant therapeutic effect and preventing the intermittent peaks and troughs associated with conventional dosing regimens
3Quantity of substance
If nitric oxide is delivered systemically to enhance NO levels in the vasculature, then endothelial dysfunction is treated, but the short lifetime of the NO molecule and limited access to the circulation prevent effective delivery
Solution Approach 1:
The patent uses transdermal delivery as an intermediary pathway to overcome the limited access to circulation for nitric oxide. The skin serves as a favorable route that bypasses the constraints of direct systemic administration, allowing NO or NO precursors to enter circulation more effectively and reach the vasculature where they can exert therapeutic effects on endothelial function
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
The formulation effectively increases systemic NO levels, restores vascular integrity, and prevents endothelial dysfunction, offering treatments for various conditions including inflammatory diseases, endothelial dysfunction, and COVID-19 complications, while minimizing side effects.
Implementation Method 1
The agent delivered via the formulation disclosed herein is able to enhance systemic nitric oxide levels in the endothelium... Sustained transdermal systemic delivery can also be achieved to harness the therapeutic potential of NO
Implementation Method 2
either by boosting the NO production or by releasing NO into the circulation
Implementation Method 3
The presented strategy also restores the integrity of the glycocalyx which allows for the resumption of flow mediated regulation of NO activity and the preservation of vascular integrity
Data Source
AI summary
A transdermal formulation for the delivery of a nitric oxide booster or nitric oxide precursor to a subject is provided. The formulation can be applied to the treatment of various diseases or conditions by enhancing systemic level of nitric oxide.