Blood Storage Compositions for Systemic Nitric Oxide Delivery
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Solution Overview
Problem
Existing therapeutic agents face bioavailability issues due to low solubility, poor uptake, and rapid elimination, limiting their effective delivery to targeted sites, and systemic delivery of nitric oxide (NO) is challenging due to its short lifetime and limited circulation access.
Innovation Solution
A transdermal formulation combining curcuminoids and senolytic flavonoids, such as quercetin and apigenin, with a polyol and fatty acid, is used to deliver active agents directly into the bloodstream, bypassing the gut and liver, enhancing systemic NO production and reducing CD38 levels to combat endothelial dysfunction and inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If therapeutic agents are administered orally or intravenously, then systemic delivery is achieved, but bioavailability is limited due to low solubility, poor gut uptake, and rapid liver elimination
Solution Approach 1:
The patent uses red blood cells as intermediary carriers to deliver therapeutic agents directly to target sites. The RBCs act as a mediator that protects the therapeutic agent from liver metabolism and enhances delivery to specific tissues, thereby improving bioavailability without requiring traditional oral or IV administration routes.
Solution Approach 2:
The patent leverages the natural properties of red blood cells, which already circulate throughout the body and have inherent ability to deliver oxygen and nutrients. By loading therapeutic agents onto RBCs, the body's existing circulatory system serves the dual purpose of transporting both native RBC functions and the therapeutic payload, eliminating the need for separate delivery infrastructure.
2Reliability
If nitric oxide is supplemented systemically, then endothelial dysfunction is reversed, but the short lifetime of NO limits its circulation access and delivery efficiency
Solution Approach 1:
The patent loads nitric oxide or nitric oxide-releasing compounds onto red blood cells in advance before transfusion. This preliminary loading allows the RBCs to serve as reservoirs that can release NO gradually at the target site, overcoming the short half-life of free NO by pre-positioning the therapeutic agent close to where it is needed.
Solution Approach 2:
Red blood cells serve as an intermediary carrier for nitric oxide, protecting it from rapid degradation in the circulation. The RBC membrane and intracellular environment provide a protective matrix that extends the functional lifetime of NO while maintaining its ability to reverse endothelial dysfunction when released at the appropriate location.
3Reliability
If CD38 levels are elevated, then NAD+ degradation increases leading to vascular senescence, but directly targeting CD38 systemically is challenging due to delivery limitations
Solution Approach 1:
The patent utilizes the natural homing ability of red blood cells to deliver therapeutic agents directly to vascular tissues. By loading CD38-targeting compounds or NAD+ precursors onto RBCs, the delivery system leverages the RBCs' inherent ability to interact with the vascular endothelium, making the targeting process occur naturally without requiring complex external guidance mechanisms.
Data Source
AI summary
Formulations comprising one or more active agents for blood storage and transfusions are provided. Also provided methods for prolonging viability of blood and enhancing efficacy of blood transfusion.