Porous Multi-Layer Microstructures for Sustained Drug Release
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Solution Overview
Problem
Wet spun microfiber-based drug delivery systems experience rapid drug release due to drug trapping on the surface during encapsulation, leading to initial burst and toxicity issues, especially for therapeutics with narrow therapeutic ranges, and there is a need for techniques that slow down the release of hydrophilic therapeutics.
Innovation Solution
Development of porous multi-layer polymeric microstructures with a therapeutic agent encapsulated in an inner core, utilizing a wet spinning process that increases the degree of crystallinity by controlling the solubility parameters of solvents and non-solvents to modulate the rate of solidification and crystallization, allowing for controlled release of dexamethasone and other agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If wet spun microfiber-based drug delivery systems are used, then drug delivery capability is provided, but rapid drug release occurs due to drug trapping on the surface during encapsulation
Solution Approach 1:
The microstructure is divided into multiple layers with distinct functions: a hydrophobic inner core for drug encapsulation and a hydrophilic outer layer for controlled release. This segmentation prevents drug trapping on the surface while enabling sustained release kinetics through the layered architecture.
Solution Approach 2:
Different regions of the microstructure are assigned different material properties: the inner core uses hydrophobic polymers to encapsulate hydrophilic drugs, while the outer layer uses hydrophilic polymers to control release. This local differentiation of material properties resolves the contradiction between encapsulation and controlled release.
2Reliability
If drug is encapsulated in wet spun microfibers, then therapeutic delivery is achieved, but initial burst release causes toxicity for therapeutics with narrow therapeutic ranges
Solution Approach 1:
The drug is pre-encapsulated within the hydrophobic inner core during the wet spinning process, creating a barrier that prevents direct contact with the external environment. This preliminary encapsulation action eliminates the initial burst release that would otherwise cause toxicity.
Solution Approach 2:
The hydrophobic inner core acts as an intermediary barrier between the hydrophilic drug and the hydrophilic outer layer. This intermediary structure controls the release kinetics by preventing direct diffusion of the drug to the surface, thereby eliminating burst release and associated toxicity.
3Ease of manufacture
If wet spinning process is used for encapsulation, then microfiber formation is achieved, but drug release cannot be slowed down
Solution Approach 1:
The wet spinning process produces composite microfibers with a core-shell structure using immiscible polymers. The hydrophobic core material and hydrophilic shell material work together to provide both ease of manufacture through standard wet spinning and prolonged drug release duration through the composite architecture.
Solution Approach 2:
The invention changes the physical and chemical parameters of the spinning system by using immiscible polymer-solvent combinations. This parameter change enables the formation of a stable core-shell structure during wet spinning that inherently provides sustained release kinetics without requiring post-processing modifications.
4Stability of the object's composition
If multi-layer polymeric microstructure with increased crystallinity is used, then controlled release is achieved, but manufacturing complexity increases
Solution Approach 1:
The wet spinning process itself generates the multi-layer crystalline structure through the phase separation and solidification of immiscible polymer solutions. The structure forms self-organizing during the spinning process without requiring additional manufacturing steps, thereby achieving controlled release profiles while minimizing manufacturing complexity.
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 method achieves prolonged drug delivery with sustained release profiles over several weeks, maintaining structural integrity and reducing toxicity by encapsulating therapeutics within the microstructure, ensuring controlled release and prolonged therapeutic efficacy.
Implementation Method 1
wet spinning the material by phase inversion, thereby producing the microstructure
Implementation Method 2
modulate the rate of solidification and crystallization
Data Source
AI summary
Methods, compositions, systems, devices and kits are provided for preparing and using a multi-layer polymeric microstructure composition for delivering a therapeutic agent to a subject. In various embodiments, the therapeutic agent includes at least one selected from the group of: a drug, a protein, a sugar, a carbohydrate, and a nucleotide sequence. In related embodiments, the composition is a fiber, a suture, a sphere, an implant, or a scaffold.