| Popis: |
Stimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously demonstrated that native ROS are capable of crosslinking and immobilizing acrylated polyethylene glycol diacrylate (PEGDA) networks and coupled payloads in tissue mimics, providing evidence for a potential targeting mechanism. To build on these promising results, we evaluated PEG dialkenes and dithiols as alternative polymer chemistries for targeting. The reactivity, toxicity, crosslinking kinetics, and immobilization potential of PEG dialkenes and dithiols were characterized. Both the alkene and thiol chemistries crosslinked in the presence of ROS, generating high molecular weight polymer networks that immobilized fluorescent payloads in tissue mimics. Thiols were especially reactive and even reacted with acrylates in the absence of free radicals, and this motivated us to explore a two-phase targeting approach. Delivering thiolated payloads in a second phase, after the initial polymer net formation, allowed greater control over the payload dosing and timing. Two-phase delivery combined with a library of radical-sensitive chemistries can enhance the versatility and flexibility of this free radical-initiated platform delivery system. |
