Polyglyoxylamide hydrogels for the traceless stimulus-mediated release of covalently-immobilized drugs†

Abstract

Hydrogels can be used in a wide range of applications from personal care products to drug delivery vehicles. Particularly for drug delivery, it is desirable to control the release of the loaded cargo as well as the hydrogel degradation time. Self-immolative hydrogels have been recently investigated to enable the stimulus-mediated breakdown of the hydrogel, which can also modulate to some extent the release of loaded drugs. However, when the drug was loaded into the hydrogel using non-covalent interactions, the background release rate of the drug in the absence of the stimulus was relatively rapid. Thus, we report here a new hydrogel system based on an acetal end-capped self-immolative polyglyoxylamide backbone with photo-responsive linkers as pendent groups to enable the covalent conjugation of amine-functionalized drugs. Using phenylalanine methyl ester as a model drug, we showed that hydrogels were successfully prepared with 96% equilibrium water content and a compressive modulus of 5.5 kPa. Light irradiation stimulated the rapid and traceless release of the model drug, while no detectable release was observed without irradiation. Furthermore, the PGAm backbone depolymerized selectively at mildly acidic pH. This system therefore provides a new hydrogel platform enabling a high level of control over both hydrogel breakdown and drug release.