Core-Shell Nanoparticles via Dual Solvent Precipitation Control
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Solution Overview
Problem
Current core-shell polymer nanoparticle delivery systems face challenges with low drug loading due to differences in precipitation times of drugs and polymers, leading to aggregation and inefficient encapsulation, particularly in nanoprecipitation methods using single solvents.
Innovation Solution
A method involving a solvent system with multiple organic solvents to control the precipitation of active agents and polymers, allowing for simultaneous or sequential precipitation to optimize drug loading, where the active agent precipitates slightly before the polymer, preventing aggregation and enhancing encapsulation efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If nanoprecipitation method using single solvent is used, then the process is simple and straightforward, but the drug loading efficiency is low due to differences in precipitation times of drug and polymer
Solution Approach 1:
The patent changes the solvent system from a single solvent to a dual solvent system consisting of a good solvent and a poor solvent for the polymer. This parameter change allows independent control of drug and polymer precipitation times, enabling the drug to precipitate first followed by polymer encapsulation, thereby achieving high drug loading efficiency (over 50%) while maintaining process simplicity
Solution Approach 2:
The patent applies preliminary action by first dissolving both drug and polymer in the good solvent, then adding the poor solvent to trigger sequential precipitation. The drug precipitates first as small nuclei, and the polymer subsequently precipitates around these nuclei, forming core-shell structures. This preliminary dissolution step ensures proper sequencing of precipitation events, resolving the contradiction between process simplicity and drug loading efficiency
2Manufacturing precision
If fast mixing is used to encourage short precipitation time, then uniform and monodispersed nanoparticles are formed, but drug loading remains low due to aggregation of precipitated drug
Solution Approach 1:
The patent changes the solvent quality parameters by introducing a poor solvent that selectively triggers drug precipitation before polymer precipitation. This parameter change creates a controlled precipitation sequence where drug nuclei form first, followed by polymer shell formation, achieving both high drug loading and uniform nanoparticle morphology without requiring extremely fast mixing
Solution Approach 2:
The patent applies dynamics by controlling the precipitation process to occur in a specific temporal sequence: drug precipitation first, then polymer precipitation. This dynamic control of precipitation timing, achieved through the dual solvent system, allows the formation of uniform core-shell structures with high drug loading, resolving the contradiction between manufacturing precision and drug loading efficiency
3Loss of time
If drug precipitates faster than polymer, then precipitation time is reduced, but precipitated drug forms larger aggregate structures leading to very low drug loading in nanoparticles
Solution Approach 1:
The patent changes the solvent system parameters by selecting a poor solvent that creates an appropriate precipitation time difference: drug precipitates first to form small nuclei, then polymer precipitates around these nuclei. This controlled parameter change prevents drug aggregation into large structures while maintaining short overall precipitation time, achieving high drug loading efficiency
Solution Approach 2:
The patent applies preliminary action by first establishing the drug precipitation event, creating small drug nuclei that serve as templates for subsequent polymer precipitation. This preliminary drug precipitation step, controlled through the dual solvent system, prevents later aggregation and ensures high drug loading in the final nanoparticles, resolving the time-efficiency contradiction
4Manufacturing precision
If polymer precipitates prior to drug, then nanoparticle formation is initiated, but drug loading will be extremely low
Solution Approach 1:
The patent changes the solvent quality parameters by selecting a poor solvent that reverses the conventional precipitation sequence. Instead of polymer precipitating first, the parameter change ensures drug precipitates first to form nuclei, followed by polymer precipitation around these nuclei. This parameter change achieves both controlled nanoparticle formation and high drug loading, resolving the contradiction between manufacturing precision and drug loading efficiency
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 approach achieves higher drug loading efficiencies, up to 50% or more, with stable and uniform nanoparticle formation, improving the delivery of hydrophobic drugs by ensuring optimal matching of precipitation times and polymer properties, thereby enhancing therapeutic efficacy.
Implementation Method 1
mixing the active solution with at least one antisolvent to precipitate the active agent and the polymer
Implementation Method 2
dissolving a polymer and an active agent in a solvent system, the solvent system comprising at least two organic solvents
Data Source
AI summary
A method of forming a core-shell polymer nanoparticle encapsulating an active agent is disclosed, including the use of a multi-solvent system in which to dissolve the active agent and a polymer prior to their precipitation using an antisolvent. The preferred use of an organic solvent system comprising two or more organic solvents allows for a high degree of control, as compared with the use of a single solvent, and enables the active agent to be precipitated more or less simultaneously with, or just prior to, the polymer.