Polymer Nanocapsules for Systemic RNAi Delivery in Cerebral Ischemia
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Solution Overview
Problem
Current treatments for brain ischemia, particularly through systemic delivery of microRNA, face challenges in delivering miRNA effectively to treat ischemic diseases due to poor delivery efficiency and invasive methods, with existing viral and non-viral vectors being ineffective.
Innovation Solution
Development of nucleic acid nanocapsules that encapsulate microRNA molecules, allowing for effective systemic delivery to brain ischemia sites, enhancing delivery efficiency and targeting specificity through polymer nanocapsules with a cross-linked polymer shell.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If systemic delivery of microRNA is used to treat brain ischemia, then the acceptability and ease of operation are improved, but the delivery efficiency and therapeutic efficacy deteriorate
Solution Approach 1:
The patent employs a polymer nanoparticle vector as an intermediary carrier to deliver microRNA molecules systemically. The nanoparticle encapsulates the microRNA, protecting it from degradation and facilitating its transport across the blood-brain barrier to reach ischemic brain tissue. This mediator approach enables systemic administration (improving ease of operation) while achieving effective delivery to the target site (maintaining delivery efficiency).
Solution Approach 2:
The patent modifies the physical and chemical parameters of the microRNA delivery system by formulating it into polymer nanoparticles with specific size, charge, and surface properties. These parameter changes enable the microRNA to be delivered systemically with improved stability and targeting capability, resolving the contradiction between ease of administration and delivery efficiency.
2Reliability
If local administration of microRNA is used to treat brain ischemia, then the delivery efficiency and therapeutic efficacy are improved, but the device complexity and operational difficulty increase due to requiring multiple injections
Solution Approach 1:
The polymer nanoparticle delivery system is designed with multi-functionality: it can be administered through a single systemic injection, protects the microRNA from degradation, facilitates blood-brain barrier penetration, and enables targeted delivery to ischemic regions. This universal platform eliminates the need for multiple invasive injections while maintaining high delivery efficiency.
Solution Approach 2:
The nanoparticle acts as an intermediary that enables single-injection systemic delivery to reach brain tissue effectively. Instead of requiring direct local injections into the brain, the nanoparticle mediator transports the microRNA through the bloodstream to the target site, simplifying the procedure while maintaining delivery efficiency.
3Reliability
If viral vectors are used for systemic delivery of microRNA, then the delivery efficiency is improved, but the safety and toxicity profile deteriorate
Solution Approach 1:
The patent employs non-viral polymer nanoparticles as disposable, biodegradable carriers for microRNA delivery. These synthetic particles avoid the immunogenicity and safety concerns of viral vectors while providing sufficient delivery efficiency. The polymer materials can be designed to degrade after delivering their cargo, eliminating long-term toxicity concerns.
Solution Approach 2:
The delivery system uses composite polymer materials that combine biocompatibility, biodegradability, and effective microRNA encapsulation capabilities. This composite approach provides an alternative to viral vectors, achieving delivery efficiency without the associated safety and toxicity problems.
Data Source
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AI summary
Provided herein are novel methods of treating cerebral ischemia, comprising administering a polymer nanocapsule or a composition thereof. Said nanocapsules comprise a polymer shell and an RNAi (e.g., miRNA) molecule, wherein the polymer shell comprises a) at least one positively charged monomer, b) at least one degradable cross-linker, and c) at least one neutral monomer; and the RNAi molecule provides therapeutic benefits to a subject suffering from cerebral ischemia. Also disclosed herein are compositions of said polymer nanocapsules.