Unit-Type Polyion Complex for Nucleic Acid Delivery
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Solution Overview
Problem
Existing nucleic acid therapeutics face challenges in achieving stable delivery due to low in vivo stability and the need for precise charge balancing between nucleic acids and block copolymers, making it difficult to design unit-type polyion complexes effectively.
Innovation Solution
A unit-type polyion complex comprising a specific number of block copolymers with a poly(ethylene glycol) segment and a cationic poly(amino acid) segment, where the total positive charges from the cationic poly(amino acid) segment are not offset by the negative charges from the nucleic acid, allowing for improved blood retention properties without requiring strict charge balancing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the positive charges from cationic poly(amino acid) segment are offset by negative charges from nucleic acid to form electrically neutral unit-type polyion complex, then the blood retention properties of nucleic acids are improved, but the design complexity increases due to requiring precise charge balancing
Solution Approach 1:
The patent changes the charge balance parameter from electrically neutral (charges offset) to electrically non-neutral (charges not offset), specifically designing the cationic poly(amino acid) segment to have excess positive charges. This parameter change simplifies the design by eliminating the need for precise charge balancing while maintaining improved blood retention properties through the non-neutral charge state.
2Stability of the object's composition
If precise charge balancing is required between nucleic acid and block copolymer to form stable unit-type polyion complex, then the structural stability is improved, but the ease of manufacture decreases due to careful design requirements
Solution Approach 1:
The patent changes the charge balance parameter from balanced to non-balanced, designing the block copolymer with excess cationic charge. This eliminates the need for precise charge balancing calculations and adjustments during manufacturing, significantly easing the design and production process while maintaining structural stability through the defined non-neutral composition.
3Reliability
If the block copolymer is designed with specific charge balancing to form unit-type polyion complex, then the therapeutic efficacy is improved through stable nucleic acid delivery, but the device complexity increases due to careful molecular design
Solution Approach 1:
The patent changes the charge balance parameter in the block copolymer design from balanced to non-balanced, with the cationic poly(amino acid) segment having excess positive charges. This parameter change simplifies the molecular design by eliminating complex charge balancing requirements while maintaining therapeutic efficacy through stable unit-type polyion complex formation with non-neutral charges.
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 simplifies the design of unit-type polyion complexes and enhances their blood retention properties, enabling effective delivery of nucleic acids by maintaining stability and protection even when the charges are not counterbalanced, thereby improving therapeutic efficacy.
Implementation Method 1
one known drug delivery technology for nucleic acids utilizes a block copolymer having a hydrophilic polymer segment and a cationic polymer segment to form a complex (polyion complex) with nucleic acid via electrostatic interactions
Data Source
AI summary
A unit-type polyion complex for use in delivering nucleic acid to a target site in a patient includes one or more molecules of a block copolymer having a poly(ethylene glycol) segment and a cationic poly(amino acid) segment and one or more molecules of a nucleic acid. A total quantity of positive charges derived from side chains of the cationic poly(amino acid) segment of the block copolymer in the unit-type polyion complex is not offset by a total quantity of negative charges derived from the nucleic acid. Furthermore, the nucleic acid has a strand length of 10-50 bases, the molecular weight of the poly(ethylene glycol) segment is 40×103 or more, and the block copolymer has a binding constant (Ka) for the nucleic acid of 3.0×105 or more.