Polysarcosine-based surfactants: syntheses and properties.

Area of Science:

• Materials Science
• Polymer Chemistry
• Biomedical Engineering

Background:

• Amphiphilic molecules form micelles to enhance hydrophobic drug solubility and absorption.
• Tocopheryl polyethylene glycol succinate (TPGS) is a common surfactant but has limitations including immunogenicity and poor biocompatibility.
• Polysarcosine (pSar) is a promising alternative to polyethylene glycol (PEG) due to its superior properties.

Purpose of the Study:

• To develop novel polysarcosine (pSar)-based amphiphilic surfactants as alternatives to TPGS.
• To conjugate hydrophobic building blocks onto pSar using two distinct polymerization strategies.
• To evaluate the drug solubilization, biocompatibility, and hemolysis of the new pSar surfactants.

Main Methods:

• Synthesized pSar conjugates via direct initialization using DSPE and DOPE as initiators.
• Prepared pSar conjugates through post-polymerization modification, esterifying pSar with VE and DMG.
• Precisely controlled pSar block polymerization degrees (14, 25, 28) and characterized critical micelle concentrations (CMC).

Main Results:

• Developed DSPE-pSar, DOPE-pSar, VE-pSar, and DMG-pSar surfactants with CMCs ranging from 0.28 to 5.63 µg/mL.
• VE-pSar significantly enhanced paclitaxel (PTX) solubility by 30-fold compared to TPGS.
• pSar surfactants demonstrated high cytocompatibility and low hemolysis rates (<5%), outperforming TPGS.

Conclusions:

• Two novel pSar-based surfactant synthesis strategies were successfully established.
• The developed pSar surfactants exhibit superior drug solubilization and biocompatibility profiles.
• These pSar conjugates hold significant promise as a new generation of clinical solubilizers for hydrophobic drugs.