PEG-Modified Carbonate Apatite Particles for Selective Drug Accumulation
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Solution Overview
Problem
Existing drug delivery systems based on carbonate apatite particles face challenges with high accumulation in normal organs like the liver, spleen, and lung, despite efforts to reduce particle size, leading to safety concerns for human medical applications.
Innovation Solution
The development of carbonate apatite particles with an average size of 500-1000 nm, formed in the presence of a PEG derivative with one or more carboxylic acids at the ends, which are taken up during particle formation, enhancing selective accumulation in target tissues and reducing normal organ uptake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If carbonate apatite particles are used for drug delivery, then nucleic acid transfection efficiency is improved, but accumulation in normal organs such as liver occurs
Solution Approach 1:
The patent applies local quality by modifying the surface properties of carbonate apatite particles specifically to interact with E-selectin, which is locally expressed on activated endothelial cells at inflammation sites. This targeted surface modification enables selective accumulation at the target site while reducing non-specific accumulation in normal organs like the liver.
Solution Approach 2:
The patent introduces E-selectin as an intermediary mechanism between the drug delivery system and the target tissue. By designing particles that specifically bind to E-selectin, the system leverages this endogenous biomarker to achieve selective targeting, thereby improving transfection efficiency at the target while minimizing off-target accumulation.
2Object-affected harmful factors
If particle size is reduced to improve circulation, then vascular embolism is prevented, but accumulation in target tissues decreases
Solution Approach 1:
The patent optimizes the particle size parameter to a specific range (50-500 nm) that balances two opposing requirements: small enough to prevent vascular embolism and circulate systemically, yet large enough to accumulate efficiently in target tissues through E-selectin binding. This precise parameter control resolves the contradiction between safety and efficacy.
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 new drug delivery system achieves higher therapeutic effects in target tissues with significantly lower drug amounts while minimizing accumulation in normal organs, ensuring safety and efficacy.
Implementation Method 1
A calcium phosphate co-precipitation method is known as a method for non-viral nucleic acid transfection into cells
Implementation Method 2
The present inventors have succeeded in finely dispersing conventional carbonate apatite particles to an average particle size of 50 nm or below by ultrasonication using an ultrasonic cleaner
Implementation Method 3
formed in the presence of a PEG derivative with one or more carboxylic acids at the ends, which are taken up during particle formation
Data Source
AI summary
The present invention provides a safe and effective DDS technique that realizes higher accumulation in lesions and reduced accumulation in normal organs including the liver, and thus can afford sufficient therapeutic effects with smaller amounts of drugs. Specifically, a composition containing carbonate apatite particles loaded with a drug, wherein the particles have an average particle size of larger than 500 nm and not more than 1000 nm, primary particles are formed in the presence of a polyethylene glycol (PEG) derivative having one or more carboxylic acids or derivatives thereof or salts thereof at the ends thereof, and the PEG derivative is taken up in the primary particles, is provided.