Figure 3. Characterization of hydrogel formulations illustrating pseudo-surfactant formation.

a Molecular dynamics (MD) simulation of the P407 self-assembly into micelles in water, with poly(ethylene glycol) blocks shown in blue and poly(propylene glycol) blocks shown in red. The water solvent is shown as translucent surface. Inset: possible micellar conformations of ML and ciprofloxacin, shown in green and yellow respectively, that were extracted from the MD simulations for further analysis in [b] and [c].

b Illustration of the complexation between ML and ciprofloxacin predicted from density functional theory (DFT) calculation. Hydrogens not involved in hydrogen-bonding have been omitted for clarity.

c Non-covalent interaction (NCI) analysis reveals a hydrogen bonding (black arrow) between ML’s carbonyl group and ciprofloxacin’s secondary amine group, and π-alkyl interactions between ML’s alkyl chain and ciprofloxacin’s quinolone ring.

d SAXS traces at 35 °C showing unchanged micelle radius, R_mic, with the addition of either 4% w/v ciprofloxacin or 2% w/v ML to an 18% w/v P407 solution, whereas the addition of both increased the lattice size and the corresponding R_mic. All formulations formed an FCC lattice, as indicated by black triangles.

e R_mic as a function of the ML concentration in formulations containing 18% w/v P407 and 4% w/v ciprofloxacin, where R_mic was determined via SAXS (see SI for the SAXS data). Dashed line indicates a 1:1 molar ratio of CIP:ML. Data was replicated using fresh samples on a lab-source Ganesha SAXS instrument and qualitatively matches that presented here (Figure S9.1, Supplementary Information)

f Rheology data showing similar gelation temperatures and gel moduli for formulations containing ciprofloxacin and ML.