Reconstituted Apolipoprotein B Lipoparticle Drug Carrier
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current drug delivery systems face challenges in transporting lipophilic drugs and contrast media due to their hydrophobic nature, which makes them difficult to be effectively delivered in physiological conditions, and there is a lack of understanding in the synthesis pathways of low-density lipoproteins (LDL) that could be exploited for targeted cancer therapy.
Innovation Solution
A method for preparing reconstituted apolipoprotein B lipoparticles by dissolving apolipoprotein B and lipids in a buffer with amphiphilic compounds and urea, followed by dialysis to reduce urea and amphiphilic compound concentrations, allowing for the incorporation of hydrophobic substances like superparamagnetic iron oxide nanoparticles and lipophilic drugs, forming a stable carrier that mimics LDL for targeted drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If lipophilic drugs and hydrophobic contrast media are used for drug delivery, then therapeutic effect and imaging capability are improved, but their hydrophobic nature makes them difficult to transport in physiological conditions
Solution Approach 1:
The patent uses reconstituted LDL particles as intermediary carriers to transport hydrophobic drugs and contrast media. The LDL particle structure, composed of apolipoprotein B and lipids, serves as a natural vehicle that can incorporate hydrophobic substances while maintaining compatibility with physiological conditions, thereby resolving the contradiction between delivery effectiveness and transportability
Solution Approach 2:
The patent employs parameter changes in the buffer system during reconstitution, specifically using amphiphilic compounds and urea in controlled concentrations, followed by dialysis to reduce these concentrations. This gradual parameter adjustment allows proper folding and assembly of apolipoprotein B into functional LDL particles that can effectively carry hydrophobic cargo
2Adaptability or versatility
If LDL synthesis pathways are understood and utilized for targeted therapy, then cancer treatment specificity is improved, but the complexity of LDL structure and assembly remains challenging
Solution Approach 1:
The patent applies preliminary action by pre-dissolving apolipoprotein B in a denaturing buffer containing amphiphilic compounds and urea before assembly. This preliminary preparation step ensures the protein is in the correct state for subsequent folding and assembly into LDL particles, simplifying the overall process despite the inherent complexity
Solution Approach 2:
The patent utilizes phase transitions during the reconstitution process, specifically the transition from denatured protein in high urea/amphiphile conditions to folded functional protein during dialysis. This controlled phase transition through buffer exchange enables the complex assembly process to proceed systematically
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 reconstituted apolipoprotein B lipoparticles effectively deliver hydrophobic substances, such as cancer drugs and contrast media, by utilizing the natural LDL receptor-mediated endocytosis pathway, demonstrating stability, non-toxicity, and efficient cellular uptake, with potential for targeted cancer therapy and imaging applications.
Implementation Method 1
dissolving apolipoprotein B and lipid in a first buffer containing 1 wt % to 15 wt % amphiphilic compounds and 2M to 8M urea to form a mixture
Implementation Method 2
dialyzing the mixture against a second buffer for 1 to several times to reduce the concentrations of the urea and the amphiphilic compound in the mixture
Implementation Method 3
dissolving apolipoprotein B and lipid in a first buffer containing 1 wt % to 15 wt % amphiphilic compounds
Implementation Method 4
containing 1 wt % to 15 wt % amphiphilic compounds and 2M to 8M urea to form a mixture
Implementation Method 5
Apolipoprotein B on the LDL is recognized by the LDL receptors and internalized in the cell
Data Source
AI summary
The present invention provides a method for preparing a reconstituted apolipoprotein B lipoparticle and the method comprises steps of (a) dissolving an apolipoprotein B and a lipid in a first buffer containing 2 M to 8 M urea and 1 wt % to 15 wt % amphiphilic compounds to form a mixture; and (b) dialyzing the mixture against a second buffer containing 0 M to 2M urea and 0 wt % to 0.5 wt % amphiphilic compounds for 1 to several times for lowering concentrations of the urea and the amphiphilic compounds in the mixture. The present invention further provides an apolipoprotein B lipoparticle and a use for the production of an apolipoprotein B lipoparticle used for delivering a hydrophobic substance.