Multilayer Biodegradable Microparticles for Sustained Drug Release
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Solution Overview
Problem
Current methods for forming microparticles for controlled release of therapeutic agents often result in initial burst release and increased drug release rates due to drug pockets formed during solvent evaporation, leading to unsustained delivery of therapeutic agents.
Innovation Solution
The formation of multilayer microparticles using poly(lactic-co-glycolic acid) (PLGA) polymers with varying molecular weights and solvents, where outer layers act as barriers to control the initial burst release and subsequent release rate of therapeutic agents, achieved by depositing and evaporating compositions on a solid surface in a controlled manner.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If microparticles are formed using conventional methods with solvent evaporation, then microparticles can be produced, but initial burst release and increased drug release rates occur due to drug pockets formed during solvent evaporation
Solution Approach 1:
The microparticle is divided into multiple layers with different polymer molecular weights. The outer layer uses higher molecular weight polymer to prevent drug pockets, while the inner layer uses lower molecular weight polymer for sustained release. This segmentation resolves the contradiction by creating functional zones that address both uniformity and controlled release performance.
Solution Approach 2:
Different regions of the microparticle are assigned different properties: the outer layer has higher molecular weight polymer for structural integrity and preventing drug pockets, while the inner layer has lower molecular weight polymer for controlled drug release. This local differentiation resolves the contradiction between uniform drug distribution and reliable controlled release.
2Reliability
If outer polymer layers are added to control burst release and reduce subsequent release rate, then sustained release is achieved, but the structure becomes more complex
Solution Approach 1:
The microparticle uses a composite structure with multiple polymer layers of different molecular weights. This composite approach resolves the contradiction by combining materials with different properties to achieve sustained release while maintaining a relatively simple fabrication process using sequential deposition.
Solution Approach 2:
The microparticle structure follows a nested configuration where an inner drug-containing layer is surrounded by an outer protective layer. This nesting approach resolves the contradiction by providing the necessary complex functionality through a hierarchical structure that can be fabricated through sequential layer deposition.
3Reliability
If higher molecular weight polymers are used in outer layers, then burst release is reduced and release rate is controlled, but the manufacturing process requires multiple deposition steps
Solution Approach 1:
The outer layer with higher molecular weight polymer is deposited first to establish the structural framework and prevent drug pockets before the inner drug-containing layer is added. This preliminary action resolves the contradiction by ensuring release rate control is built into the structure during fabrication, allowing for efficient subsequent steps.
Solution Approach 2:
The fabrication process uses continuous sequential deposition where each layer is deposited and dried in succession without breaking the workflow. This continuous action resolves the contradiction by maintaining high productivity through an streamlined multi-step process that builds the complex structure efficiently.
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
This method effectively reduces initial burst release and sustains the release of therapeutic agents over an extended duration, providing a controlled and prolonged delivery of drugs such as small molecules, peptides, and proteins.
Implementation Method 1
The polymer outer layers can act as barriers in controlling the initial burst release of the therapeutic agent and further reduce its subsequent release rate from the inner layer of the microparticle
Implementation Method 2
forming a layer comprising a first polymer on a solid planar surface that is the base of a well by depositing a first composition one or more times on the solid surface, wherein the first composition comprises the first polymer and a first solvent, and evaporating the first solvent in the first composition
Data Source
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AI summary
Microparticles are prepared by a method that includes: (a) forming a layer comprising a first polymer on a solid surface by depositing a first composition one or more times on the solid surface, wherein the first composition comprises the first polymer and a first solvent, and evaporating the first solvent in the first composition; (b) forming one or more layers comprising a second polymer and a therapeutic agent by depositing a second composition on all or part of the layer formed in step (a), wherein the second composition comprises the second polymer, the therapeutic agent, and a second solvent; and evaporating the second solvent in the second composition; and (c) forming an additional layer comprising a third polymer by depositing a third composition one or more times on a previously formed layer.