Crosslinked D,L-Mixed Poly(amino Acid) Micelles for Stable Drug Delivery
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Solution Overview
Problem
Current drug delivery systems face challenges with premature dissociation of polymer micelles due to biological barriers, leading to reduced in vivo circulation time and ineffective targeting of diseased tissues, resulting in toxicity to healthy cells and inadequate delivery of therapeutic agents.
Innovation Solution
Development of multiblock copolymers with a hydrophilic shell and a crosslinkable or crosslinked hydrophobic D,L-mixed poly(amino acid) inner core, which forms stable micelles that can encapsulate hydrophobic moieties and maintain structural integrity in physiological environments, allowing for prolonged circulation and targeted drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional polymer micelles are used for drug delivery, then they can encapsulate hydrophobic drugs and provide passive accumulation in diseased tissues, but they undergo premature dissociation in physiological environments leading to reduced circulation time and toxicity to healthy cells
Solution Approach 1:
The patent employs block copolymers composed of hydrophilic and hydrophobic segments that self-assemble into micelles with distinct core-shell structures. The hydrophobic core encapsulates drugs while the hydrophilic shell provides stability in physiological environments, resolving the contradiction between drug loading capability and micelle stability.
Solution Approach 2:
The patent modifies micelle properties by adjusting polymer composition, molecular weight, and block ratios to optimize the balance between stability and circulation time. Crosslinking density and shell thickness are tuned to prevent premature dissociation while maintaining prolonged circulation.
2Productivity
If polymer micelles are diluted following administration to reach target tissues, then passive accumulation in diseased tissues is achieved, but the reversible assembly forces cause premature dissociation before targeting is effective
Solution Approach 1:
The patent pre-stabilizes micelles through crosslinking or selection of copolymers with exceptionally low CMC values, ensuring they maintain structural integrity even when diluted in physiological environments. This preliminary stabilization prevents dissociation before the micelles can reach and accumulate in target tissues.
Solution Approach 2:
The patent creates micelles with heterogeneous structures where different regions have distinct properties: the core provides strong drug binding, the interface maintains assembly stability, and the shell provides steric stabilization and low CMC. This local differentiation allows the micelle to remain stable during dilution while maintaining drug delivery functionality.
3Adaptability or versatility
If amphiphilic block copolymers self-assemble to form nanoscopic carriers, then multi-functionality including cell-targeting and diagnostic capabilities is achieved, but in vivo circulation time is reduced due to biological barriers and protein adsorption
Solution Approach 1:
The patent employs polymer shells with controlled thickness and composition that provide steric stabilization against protein adsorption and biological barrier interactions. The flexible shell structure allows functionalization with targeting ligands while maintaining circulation stability.
Solution Approach 2:
The patent uses the polymer shell as an intermediary layer between the hydrophobic core/drug and the physiological environment. This shell prevents direct interaction with blood proteins and cellular components that would otherwise cause rapid clearance, while still allowing functional groups on the shell surface to mediate targeting and diagnostic functions.
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 multiblock copolymer micelles enhance the stability and circulation time of drug-loaded nanoparticles, enabling effective targeting and reduced toxicity by maintaining structural integrity and facilitating controlled release of therapeutic agents at specific tissue environments.
Implementation Method 1
amphiphilic multiblock copolymers self-assemble in aqueous solution to form nano- and micron-sized structures
Implementation Method 2
hydrophobic D,L-mixed poly(amino acid) block corresponds to the inner core
Data Source
AI summary
The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same.