Polymer-Stabilized Nanoparticles for Low Log P Drug Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for producing stable organic nanoparticles with drugs having a Log P less than 6 are unstable due to aggregation and particle growth, as flash nanoprecipitation techniques are ineffective for such compounds.
Innovation Solution
The development of nanoparticles with a spherical morphology and average diameter of 50 nm to 200 nm, incorporating a molecule with a Log P value of 3 or above, an amphiphilic diblock copolymer or surfactant, and a pharmaceutically-acceptable hydrophilic polymer, such as polyvinyl pyrrolidone, polyvinyl alcohol, or hydroxypropyl methylcellulose, using flash nanoprecipitation and co-freeze drying with a cryoprotectant.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If flash nanoprecipitation is used to produce nanoparticles with drugs having Log P less than 6, then nanoparticle formation is achieved, but the nanoparticles are unstable and undergo aggregation and particle growth
Solution Approach 1:
The patent introduces a hydrophilic polymer as an intermediary stabilizing agent that mediates between the hydrophobic drug core and the aqueous environment. This polymer adsorbs onto the nanoparticle surface, providing steric stabilization that prevents aggregation and Ostwald ripening, thereby resolving the instability issue of nanoparticles containing drugs with Log P less than 6
Solution Approach 2:
The patent creates composite nanoparticle structures consisting of a hydrophobic drug core, an amphiphilic copolymer shell, and a hydrophilic polymer stabilizing layer. This multi-layer composite structure combines the benefits of hydrophobic drug encapsulation with hydrophilic stabilization, preventing particle growth and aggregation while maintaining drug loading
2Quantity of substance
If conventional nanoparticle methods are used for drugs with Log P less than 6, then drug encapsulation is achieved, but the nanoparticles exhibit Oswald ripening and aggregation
Solution Approach 1:
The hydrophilic polymer acts as a mediator that stabilizes the interface between the hydrophobic drug and aqueous medium, preventing the thermodynamically driven Ostwald ripening process while maintaining high drug loading capacity within the nanoparticle core
Solution Approach 2:
The patent changes the surface chemistry parameters of the nanoparticle by introducing hydrophilic polymers with specific molecular weights and concentrations, which alters the interfacial energy and prevents particle aggregation, thereby maintaining both high drug loading and long-term stability
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 stabilizes nanoparticles, achieving high drug loading and maintaining particle size and morphology, thereby overcoming the instability issues associated with previous methods.
Implementation Method 1
Nanoparticles produced by FNP with drugs having a Log P lower than 6 were shown to be unstable towards aggregation and particle growth, i.e., Oswald ripening
Implementation Method 2
Flash nanoprecipitation (FNP) is a technique that has been used to produce organic nanoparticles containing drugs with a Log P greater than about 6, based on the anti-solvent precipitation principle
Implementation Method 3
The method includes co-freeze drying the nanoparticle with a cryoprotectant
Data Source
AI summary
The present invention provides organic nanoparticles that include a molecule having a Log P value of about 3 or above, an amphiphilic diblock copolymer or a surfactant, and a pharmaceutically-acceptable hydrophilic polymer. The present invention also provides methods of making these nanoparticles, e.g., by flash nanoprecipitation, with control over particle size and surface properties. The methods of the present invention provide a means for co-precipitating a water-insoluble compound with an amphiphilic stabilizer within a few milliseconds. The nanoparticles of the present invention exhibit high drug loading, e.g., 50% w/w, and can be produced with a mean particle size less than 200 nm and with a narrow particle size distribution.