Amphiphilic Cellulose Ethers Designed for Amorphous Solid Dispersion via Olefin Cross-Metathesis

Area of Science:

• Polymer Chemistry
• Materials Science
• Drug Delivery

Background:

• Designing cellulose ether amphiphiles is challenging due to harsh synthesis conditions.
• Olefin cross-metathesis offers a mild and efficient route to functionalize cellulose ethers.
• Existing methods are limited by the low degree of substitution of hydroxyl groups in ethyl cellulose.

Purpose of the Study:

• To develop new strategies for synthesizing cellulose ether-based amphiphiles with enhanced properties.
• To overcome limitations in creating amphiphilic derivatives for applications like amorphous solid dispersion (ASD).
• To improve the design space for hydrophilic cellulose ether derivatives.

Main Methods:

• Utilized methyl cellulose with a higher degree of substitution (DS(OH)) for olefin metathesis.
• Developed a homogeneous one-pot synthesis from cellulose, controlling ethyl and unsaturated alkyl group DS simultaneously.
• Explored methods for reducing unsaturation in metathesis products to enhance stability.

Main Results:

• Successfully synthesized novel cellulose ether amphiphiles with controlled degrees of substitution.
• Demonstrated two distinct approaches to access a wider range of amphiphilic derivatives.
• Showcased the potential of these derivatives as matrix polymers for amorphous solid dispersion.

Conclusions:

• The developed methods significantly expand the accessibility of cellulose ether-based amphiphiles.
• These new amphiphiles show promise for improving drug solubility and bioavailability via ASD.
• The findings pave the way for advanced functional materials in pharmaceutical and other applications.