Amphiphilic Polymer Nanoparticles for Poorly Water-Soluble Drug Solubilization
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Solution Overview
Problem
Poorly water-soluble active agents face challenges in formulation, particularly for oral administration, due to limited bioavailability caused by low aqueous solubility, which is difficult to enhance using existing methods without degrading the active ingredients.
Innovation Solution
The use of nanoparticles formed from specific amphiphilic polymers, such as polyglutamates grafted with vitamin E, that non-covalently associate with active agents, increasing their aqueous solubility while maintaining stability and biocompatibility, and allowing for controlled release profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional solubilizing additives or surfactants are used to increase aqueous solubility, then the solubility of the active ingredient improves, but the active ingredient may degrade due to exposure to organic solvents, surfactants, high temperature, or high shear stress
Solution Approach 1:
The patent uses phospholipid vesicles (liposomes) as an intermediary carrier to solubilize hydrophobic active ingredients. The liposomes encapsulate the active ingredient within their hydrophobic core, providing a protective interface between the water-soluble environment and the hydrophobic drug molecule, thereby preventing degradation while maintaining solubility
Solution Approach 2:
The patent changes the physical state and solubility parameters by forming a complex between the active ingredient and phospholipid vesicles. This transforms the hydrophobic active ingredient into a water-soluble complex through the amphiphilic nature of phospholipids, altering the solubility parameters without requiring organic solvents or extreme conditions
2Quantity of substance
If high molecular weight polymer additives are used to increase solubility, then the solubility capacity improves, but the viscosity of the formulation increases excessively, making injection difficult
Solution Approach 1:
The patent segments the solubilizing function into individual phospholipid molecules that self-assemble into small vesicular structures. Rather than using a single high molecular weight polymer, the system uses multiple low molecular weight phospholipid units that provide solubility enhancement without creating excessive viscosity, as each vesicle acts as an independent solubilizing unit
Solution Approach 2:
The patent employs phospholipid bilayer membranes forming flexible vesicular shells. These thin film structures provide a large surface area for solubilizing active ingredients while maintaining small particle size and low viscosity in the bulk formulation, enabling easy injection through small-gauge needles
3Quantity of substance
If organic solvents are used to solubilize the active ingredient, then the solubility improves, but the active ingredient may degrade due to contact with organic solvents
Solution Approach 1:
The patent introduces phospholipid vesicles as an intermediary medium that replaces organic solvents. The active ingredient is solubilized within the hydrophobic core of the liposomes formed by phospholipids, eliminating the need for direct contact with organic solvents while maintaining solubility in aqueous formulations
Solution Approach 2:
The patent changes the solubility mechanism from organic solvent-based dissolution to aqueous-based liposomal encapsulation. This parameter change allows the active ingredient to be solubilized in water without exposure to degrading organic solvents, by utilizing the amphiphilic properties of phospholipids to create a water-compatible delivery system
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 significantly enhances the solubilization of poorly water-soluble active agents, achieving high concentrations for effective administration while maintaining low viscosity and biocompatibility, and providing a regulated release profile.
Implementation Method 1
nanoparticles formed from amphiphilic polymers, such as polyglutamates grafted with vitamin E, that non-covalently associate with active agents
Implementation Method 2
nanoparticles formed from amphiphilic polymers, such as polyglutamates grafted with vitamin E, that non-covalently associate with active agents
Implementation Method 3
providing a regulated release profile
Implementation Method 4
for parenteral administration, it is desirable that the solubilizing additive be perfectly tolerated and degrade rapidly
Data Source
AI summary
The present invention relates to a composition including at least one active agent with low water solubility, said active agent being present in a form non-covalently in combination with nanoparticles made of at least one polymer POM of formula (I), and in which said active agent is present at a rate of at least 5 μmol/g of POM. The invention also relates to the use of such nanoparticles, non-covalently in combination with an active agent, with a view to increasing the water solubility of said active agent.