Polysaccharide Core-Shell Nanoparticles for Protein Delivery
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Solution Overview
Problem
Current methods for delivering protein-based therapeutics face challenges such as low loading efficiency and uncontrollable release profiles, leading to the inactivation of biomolecules during synthesis, formulation, and delivery, which hinders their clinical translation.
Innovation Solution
The development of therapeutic particles comprising a negatively charged polysaccharide and a positively charged polysaccharide, where the positively charged polysaccharide is covalently crosslinked in the core, allowing for the efficient incorporation and stabilization of therapeutic proteins, enhancing their delivery and bioactivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If existing nanoparticle platforms are used for protein delivery, then delivery capability is provided, but loading efficiency is low and release profiles are uncontrollable
Solution Approach 1:
The patent employs composite nanoparticle structures combining multiple materials with complementary properties. The core-shell architecture uses an inner core material for protein loading and an outer shell material for controlled release, creating a composite system that simultaneously achieves high loading efficiency and controllable release profiles through the synergistic interaction of different materials.
Solution Approach 2:
The nanoparticle design implements local quality by differentiating functional properties across different regions of the particle. The core region is optimized for high protein loading capacity while the shell region is engineered for controlled release kinetics, allowing each region to perform its specific function optimally without compromising the other.
2Ease of manufacture
If synthetic chemical coupling and formulation parameters (homogenization, sonication, extrusion, solvent exposure) are used, then particle formation is achieved, but biomolecules are inactivated
Solution Approach 1:
The patent replaces harsh mechanical processing methods (sonication, extrusion, homogenization) with gentler alternative approaches such as microfluidic mixing or spontaneous self-assembly. These substituted methods achieve particle formation without subjecting biomolecules to extreme mechanical stresses that cause inactivation, thereby maintaining biomolecule stability while still forming functional nanoparticles.
Solution Approach 2:
The formulation process utilizes parameter changes such as pH adjustment, ionic strength modulation, or temperature cycling to drive particle formation and biomolecule encapsulation. By carefully controlling these parameters, the system achieves effective particle formation without exposing biomolecules to conditions that would cause denaturation or inactivation.
3Reliability
If protein therapeutics are delivered to desired disease tissues, then therapeutic effect is achieved, but delivery challenges hinder clinical translation
Solution Approach 1:
The nanoparticle platform is designed with universal, multi-functional capabilities that address multiple delivery challenges simultaneously. A single particle design can provide protected transport, targeted delivery, controlled release, and stability enhancement, eliminating the need for multiple separate delivery systems and reducing overall complexity while improving delivery effectiveness to disease tissues.
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 approach achieves high incorporation efficiency of therapeutic proteins into nanoparticles, maintaining bioactivity and stability, and provides controlled release profiles, addressing the limitations of existing protein delivery methods.
Implementation Method 1
a particle comprising a negatively charged polysaccharide and a positively charged polysaccharide, wherein the core of the particle comprises the positively charged polysaccharide
Implementation Method 2
the positively charged polysaccharide is covalently crosslinked by a dicarboxylic acid linker in the core of the particle
Data Source
AI summary
The present application provides a method of making a particle comprising (i) obtaining a first solution comprising a negatively charged polysaccharide; (ii) obtaining a second solution comprising a positively charged polysaccharide; and (iii) mixing the first solution and the second solution to obtain a suspension comprising the particle. The present application also provides a method of making a therapeutic particle, comprising: (i) obtaining a solution comprising a therapeutic protein; (ii) obtaining a first suspension comprising the particle comprising a negatively charged polysaccharide and a positively charged polysaccharide, and (iii) mixing the solution of the therapeutic protein and the first suspension to obtain a second suspension comprising the therapeutic particle. The present application also provides particles (e.g., therapeutic particles) prepared by any one of the disclosed methods, as well as the compositions comprising such particles, and methods of treating a disease or condition using such particles and compositions.