Agent Delivery Membrane for Localized Immunosuppression in Transplantation
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Solution Overview
Problem
Current immunosuppressive medications used in solid organ transplantation have adverse effects on non-transplanted organs due to systemic administration, necessitating a method to deliver these agents directly to the transplanted organ while minimizing systemic exposure.
Innovation Solution
A method involving the surgical attachment of agent delivery membranes or platforms to the inner surface of fluid passageways upstream from the transplanted organ, allowing for localized delivery of therapeutic agents such as immunosuppressives directly to the organ, thereby reducing systemic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive medications are administered systemically to suppress the recipient immune system, then the desired effect of minimizing immune attack against the transplanted organ is achieved, but adverse effects on other organs such as nephrotoxicity, hepatotoxicity, and central nervous system effects occur
Solution Approach 1:
The patent applies local quality by delivering immunosuppressive agents directly to the transplanted organ through catheter-based localized administration, rather than systemic distribution. This creates a high concentration gradient at the target organ while maintaining low systemic levels, thereby achieving reliable immunosuppression at the graft site while minimizing toxic effects on distant organs such as kidneys, liver, and central nervous system
Solution Approach 2:
The patent uses an intermediary delivery system consisting of catheters positioned in vessels supplying the transplanted organ. This intermediary mechanism allows controlled local delivery of immunosuppressive agents, acting as a mediator between the drug and the target organ, enabling precise spatial and temporal control of drug distribution to achieve therapeutic effect at the graft while limiting systemic exposure
2Reliability
If higher levels of immunosuppressive medication are obtained in the transplanted organ, then donor organ acceptance and longer function are improved, but systemic levels must be reduced to minimize adverse effects
Solution Approach 1:
The patent implements local quality by establishing a localized high-concentration environment of immunosuppressive agents specifically within the transplanted organ through targeted catheter delivery. This creates a steep concentration gradient where the graft receives therapeutic levels sufficient for long-term acceptance and function, while systemic circulation maintains minimal levels to avoid toxicity
Solution Approach 2:
The patent applies parameter changes by dramatically altering the spatial distribution parameters of immunosuppressive agents - changing from uniform systemic distribution to highly localized concentration at the graft site. This parameter modification enables achieving high local concentrations (improving organ acceptance) while maintaining low systemic levels (minimizing adverse effects)
Data Source
AI summary
The present invention provides systems and methods for downstream delivery of agents. The invention includes membranes that are attachable to the inner wall of a blood vessel and deposits one or more agents into a subject's bloodstream. The invention is able to treat locations downstream from the membrane attachment site. In certain embodiments, the invention is useful in solid organ transplantation, where at the time of transplanting the organ, the membrane is attached to an artery feeding into the transplanted organ and delivers agents such as immunosuppressives and gene therapy to achieve a high level of immunosuppressive medication within the transplanted solid organ while minimizing the systemic side-effects. The invention enhances solid organ function and minimizes adverse effects, leading to a better clinical outcome for the recipients. The system and methods can also be applied to autologous vascularized composite grafts.