Modulation of Viscoelasticity and HIV Transport as a Function of pH in a Reversibly Crosslinked Hydrogel

Materials that respond to physiological stimuli are important in developing advanced biomaterials for modern therapies. The reversibility of covalent crosslinks formed by phenylboronate (PBA) and salicylhydroxamate (SHA) has been exploited to provide a pH‐responsive gel for application to the vaginal tract. Dynamic rheology reveals that the gel frequency‐dependent viscoelastic properties are modulated by pH. At pH 4.8 the viscous component dominates throughout most of the frequency range. As the pH increases, the characteristic relaxation time continues to increase while the G′Plateau levels off above pH 6. At pH 7.5, the elastic component dominates throughout the frequency sweep and is predominately independent of frequency. Particle tracking assesses the transport of both fluorescently labeled HIV‐1 and 100‐nm latex particles in the PBA–SHA crosslinked gel as a function of pH. At pH 4.8 the ensemble‐averaged mean squared displacement at lag times greater than three seconds reveals that transport of the HIV‐1 and 100‐nm particles becomes significantly impeded by the matrix, exhibiting diffusion coefficients less than 0.0002 µm2 s−1. This pH‐responsive gel thus displays properties that have the potential to significantly reduce the transport of HIV‐1 to susceptible tissues and thus prevent the first stage of male‐to‐female transmission of HIV‐1. pH modulates the viscoelasticity and HIV transport in hydrogels created by the pH‐sensitive equilibrium between polymer‐bound phenylboronic acid (PBA, blue in figure) and salicylhydroxamic acid (SHA, green in figure). At vaginal pH the PBA–SHA crosslink rapidly hydrolyzes and reforms yielding viscoelastic gels. Above pH 5.5 the rate of hydrolysis decreases resulting in more permanently covalent crosslinks and elastic gel behavior that impedes HIV transport.