Branched Polyoxyalkylene Lipids for Stable Low-Immunogenic LNPs
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Solution Overview
Problem
Existing polyethylene oxide (PEO) based lipids used in lipid nanoparticles face issues with immune response, leading to the formation of anti-PEO antibodies, which compromise the 'stealth effect' and cause allergic reactions, while also having poor storage stability.
Innovation Solution
Development of polyoxyalkylene based compounds with a different polyoxyalkylene unit, such as poly(ethylene oxide) with C1 to C3-alkyloxymethyl side chains, which undergo substitution and esterification reactions to form novel lipids with improved storage stability and reduced immunogenic potential.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polyethylene oxide (PEO) based lipids are used in lipid nanoparticles, then the 'stealth effect' is achieved to avoid recognition by the reticuloendothelial system, but immune response occurs leading to formation of anti-PEO antibodies and allergic reactions
Solution Approach 1:
The patent modifies the chemical structure of the polyoxyalkylene unit by introducing C1-C3 alkyloxymethyl side chains at specific positions in the polymer chain. This structural parameter change maintains the hydrophilic character and stealth effect while altering the molecular recognition patterns that trigger immune responses, thereby reducing antibody formation.
Solution Approach 2:
The invention creates a composite polyoxyalkylene structure combining ethylene oxide units with propylene oxide units and alkyloxymethyl side chains. This composite architecture integrates the beneficial stealth properties of PEO with modified immunogenicity characteristics, achieving both prolonged circulation and reduced immune recognition.
2Reliability
If polyethylene oxide (PEO) based lipids are used in lipid nanoparticles, then the 'stealth effect' is achieved, but storage stability is poor
Solution Approach 1:
The patent introduces structural modifications to the polyoxyalkylene chain including side chain incorporation and copolymerization sequences that enhance molecular packing and structural rigidity. These parameter changes improve storage stability by reducing molecular degradation while preserving the hydrophilic surface properties necessary for the stealth effect.
3Object-affected harmful factors
If alternative polyoxyalkylene structures are developed to reduce immunogenicity, then antibody formation is minimized, but the stealth effect may be compromised
Solution Approach 1:
The patent applies local quality modification by introducing side chains and copolymer units at specific positions within the polyoxyalkylene structure rather than uniform modification throughout. This localized structural variation reduces immune recognition at critical sites while preserving the overall hydrophilic character and stealth properties of the nanoparticle surface.
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 novel polyoxyalkylene compounds exhibit better storage stability and minimize the formation of antibodies, maintaining the 'stealth effect' and enhancing the efficacy of lipid nanoparticles as delivery vehicles for therapeutic nucleic acids.
Implementation Method 1
replacing —H by a leaving group —X, which is able to undergo a substitution reaction; thereafter performing a substitution reaction of X-A-R3
Implementation Method 2
performing an esterification reaction with wherein Y is a leaving group able to undergo a esterification reaction with —H of the —OH groups
Data Source
AI summary
The present invention refers to polyoxyalkylene based compounds and their manufacturing method as well as compositions containing at least one polyoxyalkylene based compound and at least one active agent. Furthermore, the present invention refers to the manufacture of the compositions of the present invention as well as their use for the treatment of an illness in mammals or humans.