Ionizable Lipidoid Nanoparticles for Stable Cellular Nucleic Acid Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The effective targeted delivery of biologically active substances such as small molecule drugs, proteins, and nucleic acids to cells is hindered by their instability and low cell permeability, necessitating the development of lipid-nanoparticle compositions that can deliver therapeutic agents with safety, efficacy, and specificity.
Innovation Solution
A class of lipidoid compounds with specific structures, including formulae (X), (I), and (II), are used to form lipid nanoparticles that facilitate the delivery of therapeutic agents by forming nanoparticle compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acids are delivered directly to cells, then therapeutic effect is achieved, but cell permeability is low and stability is poor
Solution Approach 1:
The patent employs lipidoid compounds formulated into lipid nanoparticle compositions that composite nucleic acids with lipid materials. This composite structure protects the nucleic acids from degradation while facilitating cellular uptake, thereby simultaneously improving stability and delivery efficacy.
2Reliability
If nucleic acids are delivered directly to cells, then therapeutic effect is achieved, but cell permeability remains low
Solution Approach 1:
The patent utilizes ionizable lipidoids that change their physical and chemical parameters based on pH. In the acidic environment of endosomes, the lipidoids become protonated and form transient pores or facilitate membrane disruption, enabling nucleic acid release into the cytoplasm and improving cellular permeability.
3Reliability
If lipid-nanoparticle compositions are developed for targeted delivery, then delivery specificity is improved, but manufacturing complexity increases
Solution Approach 1:
The patent divides the delivery system into distinct functional components: ionizable lipidoids for endosomal escape, PEGylated lipids for steric stabilization and circulation, and targeting ligands for specific cell recognition. This segmentation allows each component to perform its specialized function while simplifying the overall formulation development and manufacturing process.
Data Source
AI summary
Disclosed are lipidoid compounds having the structure of formula (X) or formulawherein the groups are as defined in the application. Also disclosed are nanoparticle compositions comprising a lipidoid of the invention that are capable of delivering a therapeutic agent. The application also discloses pharmaceutical compositions comprising a lipidoid composition of the invention.