Therapeutic Nanoparticle Drug Loading via pH Ionization
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Solution Overview
Problem
Existing nanoparticle-based drug delivery systems for histone deacetylase inhibitors, such as quisinostat, face challenges with low drug loading efficiency and poor delivery to targeted tissues, particularly in solid tumors.
Innovation Solution
A novel method for manufacturing therapeutic nanoparticles involves mixing an organic phase with an aqueous phase, adding a water-insoluble biologically active ingredient with an ionizable group, and removing the organic solvent, which enhances drug loading by increasing the ionization of the active ingredient and electrostatic interaction with the nanoparticle surface.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional nanoparticle manufacturing processes are used, then the drug delivery system can be produced, but the drug loading efficiency is low (only 1-2% for quisinostat)
Solution Approach 1:
The patent changes the pH parameter of the aqueous phase to basic conditions (pH 8-14), which increases the ionization of the weak acid drug (quisinostat) and enhances its electrostatic interaction with the nanoparticle surface, thereby improving drug loading efficiency from 1-2% to significantly higher levels
Solution Approach 2:
The patent performs preliminary ionization of the drug by adjusting the pH of the aqueous phase before nanoparticle formation. This preliminary action ensures the drug is in its ionized state during encapsulation, maximizing electrostatic interaction with the nanoparticle surface and improving loading efficiency
2Quantity of substance
If the aqueous phase pH is adjusted to basic conditions to increase drug ionization, then drug loading efficiency improves, but the complexity of the manufacturing process increases
Solution Approach 1:
The patent modifies a single key parameter (pH of aqueous phase) to basic conditions, which simultaneously achieves drug ionization and electrostatic interaction enhancement. This focused parameter change improves drug loading while adding minimal process complexity compared to conventional neutral pH methods
3Reliability
If conventional nanoparticle processes are used, then the manufacturing process is simple, but the delivery to targeted tissues is poor
Solution Approach 1:
By changing the pH parameter to basic conditions, the patent enhances drug ionization and electrostatic interaction with nanoparticle surfaces, improving drug loading efficiency. This results in better drug delivery to targeted tissues while maintaining a relatively simple manufacturing process involving only pH adjustment and standard nanoparticle formation steps
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 significantly higher drug loading efficiencies, up to 9% for quisinostat, and maintains the therapeutic potency of the drug, effectively slowing tumor growth and prolonging survival in mouse models of glioblastoma.
Implementation Method 1
a nanoparticle comprising an amphiphilic polymer
Implementation Method 2
the active ingredient comprising an ionizable group and having a partition coefficient of log P>0, wherein the active ingredient is at least partially ionized in the aqueous phase
Implementation Method 3
the active ingredient and the nanoparticle electrostatically interact
Implementation Method 4
removing the organic solvent from the mixture
Data Source
AI summary
The methods of manufacture of a drug delivery composition. In some aspects, the methods include providing an organic phase, a biologically active ingredient, and an aqueous phase with a desirable pH (e.g., a pH at which the active ingredient has increased solubility in the aqueous phase compared to at neutral pH). After mixing of one or more of the aforementioned components, the resultant mixture is processed to provide the desired drug delivery composition.