Continuous and highly variable rate controlled release of model drugs from sphingolipid-based complex high axial...

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Drug Delivery

Background:

• Sphingolipids are key components of cell membranes.
• Drug delivery systems often face challenges with drug stability and controlled release.
• Self-assembling amphiphiles offer potential for novel drug encapsulation.

Purpose of the Study:

• To synthesize novel sphingolipids with ester-linked model drugs.
• To investigate the self-assembly behavior and resulting supramolecular structures.
• To evaluate the stability and hydrolysis resistance of encapsulated drugs within these structures.

Main Methods:

• Synthesis of sphingolipids with ester-linked drugs at the ceramide core.
• Self-assembly studies below chain-melting temperatures, alone and with co-amphiphiles.
• Morphological characterization of supramolecular assemblies, including complex high axial ratio microstructures (CHARMs).
• Hydrolysis rate studies of ester-linked drugs within CHARMs versus control systems.

Main Results:

• Synthesized sphingolipids self-assembled into various morphologies, including CHARMs.
• Esters within CHARMs exhibited significantly higher resistance to hydrolysis compared to monomers or vesicles.
• Hydrolysis rates were tunable (days to years) by modifying ceramide core structure (fatty acyl chain length, ester distance).

Conclusions:

• Sphingolipid-based CHARMs provide a protective environment for ester-linked drugs.
• The tunable hydrolysis rates offer potential for controlled drug release applications.
• These microstructures represent a promising platform for developing advanced drug delivery systems.