Increasing the aqueous solubility of the anesthetic propofol through wormlike micelle formation

Abstract

Propofol, a phenol derivative, is commonly employed as an intravenous anesthetic during clinical procedures, formulated as an oil/water emulsion due to its poor solubility in water. The stability limitations associated with emulsions have prompted research efforts towards developing aqueous formulations of propofol. In this work, we investigate the solubility enhancement of propofol in anionic and cationic surfactants. Our findings reveal that the solubility of propofol can increase significantly, up to 100-fold, depending on the nature of the micellar aggregate, as observed for alkylammonium halogenates CnTAB (for n = 12, 14 and 16), contrasting with the lower solubility with SDS. Interestingly, C₁₄TAB and C₁₆TAB demonstrate significantly higher solubility than C₁₂TAB. This was attributed to the formation of wormlike micelles, in which the propofol molecules are positioned between the cationic heads of the surfactant molecules, changing the micellar curvature and the morphology of the aggregate. Therefore, the aromatic molecules in the micellar environment can be partitioned into the micellar cores and their palisades. Regarding C₁₂TAB, the alkyl chain is too short to form wormlike micelles, thus, concentrating propofol molecules mainly into the micellar core, and consequently, leading to their aggregation. Solubility diagrams of propofol were constructed in conjunction with different surfactants. The systems exhibiting viscoelastic behavior, indicative of wormlike micelle formation, were further investigated using rheology. Additionally, the fluorescent properties of propofol enabled the examination of the anesthetic molecule within diverse micellar environments.