Anionic Nanocomplex Carrier for Protein Drug Delivery
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Solution Overview
Problem
Current methods for protein drug delivery are inefficient and often damage the protein structure, leading to loss of activity, and lack a convenient and versatile approach for targeted intracellular and in vivo delivery.
Innovation Solution
A nanocomplex comprising 0-60% protein drug, 0.03-15% hyaluronic acid, 0.1-20% protamine, and 35-95% lipid components, including electrically neutral and anionic lipids, with apolipoprotein or mimetic peptides, forming a stable carrier for efficient protein delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cationic carrier materials are used to deliver proteins via electrostatic or hydrophobic interactions, then protein delivery efficiency is improved, but in vivo toxicity increases
Solution Approach 1:
The patent changes the charge parameter of the carrier material from positive (cationic) to negative (anionic) by using anionic lipids and polyanionic polymers. This parameter change maintains protein binding capability through electrostatic interaction with positively charged protein regions while eliminating the toxicity associated with cationic materials in vivo.
Solution Approach 2:
The patent creates a composite carrier system combining anionic lipids and polyanionic polymers that work synergistically. The anionic lipid provides the negative charge and membrane interaction properties, while the polyanionic polymer enhances protein binding and stabilizes the complex, achieving both efficient delivery and low toxicity.
2Adaptability or versatility
If protein modification is performed to enable binding with carrier materials, then delivery capability is improved, but protein structure and function are destroyed
Solution Approach 1:
The patent introduces an intermediary polyanionic polymer that mediates between the carrier system and the protein. This intermediary binds to positively charged regions on the protein surface through electrostatic interaction without requiring covalent modification, thus enabling delivery capability while preserving protein structure and function.
Solution Approach 2:
The patent exploits the natural charge distribution parameter of proteins, utilizing the fact that protein surfaces have partial positive regions despite overall negative or neutral charge. This allows binding to anionic carriers without modification, maintaining protein integrity while achieving delivery capability.
3Ease of operation
If complex synthesis and purification processes are used to link transmembrane peptides to proteins, then cellular uptake is improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses an anionic polymer intermediary that simplifies the process by eliminating the need for covalent attachment of transmembrane peptides. The polymer acts as a bridge that facilitates cellular uptake through electrostatic interaction with proteins, greatly reducing synthesis and purification complexity while maintaining high cellular uptake efficiency.
4Adaptability or versatility
If super-negative charging modification is performed on proteins, then binding with cationic carriers is improved, but manufacturing complexity increases
Solution Approach 1:
The patent inverts the traditional approach by instead of making proteins super-negatively charged to bind with cationic carriers, it uses naturally occurring positive regions on proteins to bind with anionic carriers. This inversion eliminates the need for complex charging modification while achieving effective binding.
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 nanocomplex enables highly efficient intracellular and in vivo delivery of proteins with minimal structural damage, achieving targeted protein delivery and maintaining biological activity.
Implementation Method 1
bind directly to target proteins via electrostatic or hydrophobic interactions
Implementation Method 2
bind directly to target proteins via electrostatic or hydrophobic interactions
Data Source
AI summary
Disclosed is a nanocomplex, a preparation method therefor, and a use thereof. The nanocomplex comprises 0-60% a protein drug, 0.03-15% hyaluronic acid, 0.8-20% protamine, 35-95% lipid components, and 2.5-40% a apolipoprotein and/or a mimetic peptide thereof; the lipid components comprise an electrically neutral lipid and an anionic lipid; and the total amount of hyaluronic acid and protamine is 0.03-15%. The nanocomplex of the present invention provides a general-type carrier for protein drugs having different physicochemical properties (such as molecular weights of 10-255 KDa and PIs of 4-11), implements highly efficient intracellular, in vivo, and even in-brain delivery, utilized technology is universal in nature, and said invention can effectively solve the current problem of insufficient in vivo and in vitro transport of protein drugs (comprising a protein drug exceeding the molecular weight and PI of an embodiment).