Impact of Surfactant Properties on Phase Transition and Morphology of Thermoresponsive Polysaccharide Biomaterials

Understanding the interactions between various surfactants and thermoresponsive polymers is essential for regulating phase transition and controlling polymer aggregation, offering opportunities in producing biomaterials with diverse morphologies and microstructures. Here we developed a new class of dextran-based thermoresponsive polysaccharides by chemically altering the hydrophilic polymer backbone into hydrophobic derivatives. These thermoresponsive materials exhibited robust, reversible phase transitions and tunable lower critical solution temperatures. Photo-initiated radical polymerization permits facile chemical crosslinking and captures phase separation dynamically, leading to the formation of hydrogels with distinct morphologies. We evaluated the effects of various surfactants – such as anionic sodium dodecyl sulfate (SDS), nonionic pluronic F-127, cationic hexadecyltrimethylammonium bromide (CTAB), and zwitterionic 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) – on the phase transition and microdomain morphology of polysaccharides. We found that temperature-triggered hydrophobic interactions and phase transition behaviors are regulated by a combination of surfactant charge density, hydrophilic—lipophilic balance (HLB) values, and critical micelle concentrations (CMC). Surfactants with higher HLB values significantly disrupt phase separation above their CMCs. Notably, the non-ionic pluronic F127 surfactant effectively eliminates phase transitions across a wide range of dextran molecular weights and concentrations even below its CMC. Depending on their charge and CMC, surfactants also modify the microdomain size, shape, and number by altering the balance between continuous and dispersed phases. These findings will expand the selection of appropriate surfactants to regulate the polymer/polymer and polymer/solvent interactions to modulate phase-separation and microstructures morphology that may serve as a potential polymeric carrier for cancer drug delivery.