Amphiphilic Triblock Copolymers for Controlled Drug Release
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Solution Overview
Problem
Current controlled release systems for therapeutically active agents face challenges such as cumbersome and expensive fabrication, irreproducible release kinetics, adverse effects from organic solvents, high viscosity leading to patient discomfort, and limited suitability for protein delivery due to loss of activity during incorporation into solid polymers, as well as rapid or slow biodegradability that does not align with desired treatment durations.
Innovation Solution
Development of amphiphilic triblock copolymers with a linear poly(ethylene glycol) central block and hydrophobic blocks comprising cyclic monomers, where 25-100% of hydroxyl end-groups are modified with fatty acid derivatives, allowing for the formation of micelles or thermo-reversible gels that can be tuned for optimal biodegradability and controlled release, maintaining protein activity and reducing administration discomfort.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional controlled release devices are used, then active agents can be delivered, but fabrication is cumbersome and expensive with irreproducible release kinetics
Solution Approach 1:
The patent modifies the chemical structure of block copolymers by changing parameters such as block length ratios, molecular weights, and end-group functionalization to achieve reproducible release kinetics. Specifically, adjusting the hydrophobic block composition and end-cap modifications allows precise control over drug release rates while simplifying fabrication processes.
Solution Approach 2:
The invention uses amphiphilic block copolymers composed of hydrophilic and hydrophobic blocks to create micellar structures that provide reproducible controlled release. The composite nature of these copolymers, with distinct functional blocks, enables reliable drug encapsulation and release kinetics while simplifying the overall device fabrication.
2Ease of manufacture
If organic solvents are used in device fabrication, then devices can be formed, but adverse effects occur on therapeutic agents and toxic residual solvent remains
Solution Approach 1:
The patent extracts and eliminates organic solvents from the fabrication process by using alternative aqueous-based methods. The block copolymer system allows device formation through self-assembly in water, removing the need for organic solvents that cause therapeutic agent degradation and leave toxic residues.
Solution Approach 2:
The amphiphilic block copolymers act as intermediaries that enable device formation without organic solvents. These copolymers self-assemble in aqueous environments to form micelles or hydrogels that can encapsulate therapeutic agents, serving as a mediator between the aqueous environment and the hydrophobic drug molecules.
3Ease of operation
If high viscosity solutions or dispersions are administered, then devices can be delivered, but patient comfort is compromised
Solution Approach 1:
The patent utilizes phase transitions of thermosensitive block copolymers that remain soluble at room temperature but gel at body temperature. This allows administration as low-viscosity aqueous solutions that are patient-friendly, which then transform into gel structures in vivo to provide controlled release without causing administration discomfort.
4Duration of action of moving object
If proteins are incorporated into solid polymers, then controlled release is achieved, but protein activity is lost
Solution Approach 1:
The patent changes the physical state parameters of the polymer system from solid to liquid/gel phase at administration temperature. This allows proteins to be delivered in a liquid vehicle that maintains protein activity, with controlled release achieved through the gel structure formation and degradation in vivo rather than through solid polymer matrix diffusion.
5Duration of action of stationary object
If biodegradable polymers are used, then devices can be eliminated after use, but degradation rate does not align with desired treatment durations
Solution Approach 1:
The patent employs parameter changes in the block copolymer structure, including varying block lengths, compositions, and end-group modifications, to precisely tune the biodegradation rate. By adjusting these parameters, the degradation profile can be matched to the desired treatment duration, whether short-term or long-term therapy is required.
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 amphiphilic triblock copolymers enable a controlled and sustained release of therapeutically active agents, maintaining protein activity, reducing patient discomfort during administration, and offering biodegradability tailored for specific treatment durations, thus addressing the limitations of existing systems.
Implementation Method 1
Such copolymers may form micelles or thermo-reversible gels in aqueous solutions that may contain at least one therapeutically active agent
Implementation Method 2
Micelles also find important applications in the solubilisation of highly water insoluble drugs, since such drugs may be incorporated in the hydrophobic core of the micelle
Implementation Method 3
Such a copolymer solution has the peculiar property that at room temperature it is water-soluble and at the body temperature of 37°C it becomes water-insoluble and forms a gel
Implementation Method 4
The composition containing the copolymer and the therapeutically active agent may be administered at room temperature as a low viscosity aqueous solution, using a small gauge needle, thus minimizing discomfort for the patient. Once at body temperature the composition will form a well-defined gel
Data Source
AI summary
The present invention relates to amphiphilic triblock copolymers B-A-B, wherein A is a linear poly(ethylene glycol) block, having a number average molecular weight (Mn) of between 900 and 3000 Daltons, determined with size exclusion chromatography; wherein B are hydrophobic blocks comprising at least two cyclic monomers selected from the group consisting of glycolide, lactide, 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, each B-block having a number average molecular weight (Mn) of between 400 and 2000 Daltons, determined with size exclusion chromatography; and wherein 25% to 100% of the polymer hydroxyl end-groups are covalently modified with at least one derivative of a C2-C20 fatty acid. The invention also relates to compositions comprising such polymers and the use thereof.