Remote‐Controlled Hydrogel Depots for Time‐Scheduled Vaccination

Abstract

Remote‐controlled drug depots represent a highly valuable tool for the timely controlled administration of pharmaceuticals in a patient compliant manner. Here, the first pharmacologically controlled material that allows for the scheduled induction of a medical response in mice is described. To this aim, a novel, humanized biohybrid material that releases its cargo in response to a small‐molecule stimulus licensed for human use is developed. The functionality of the material in mice is demonstrated by the remote‐controlled delivery of a vaccine against the oncogenic human papillomavirus type 16. It is shown that the biohybrid depot‐mediated immunoprotection is equivalent to the classical multi‐injection‐based vaccination. These results indicate that this material can be used as a universal remote‐controlled vehicle for the patient‐compliant delivery of vaccines and pharmaceuticals.

Supramolecular Polymer Networks: Preparation, Properties, and Potential

“…Weber and coworkers developed a hydrogel for time-scheduled vaccination that consists of biohybrid materials cross-linked via multiple supramolecular interactions [283]. The hydrogel is based on two eight-arm PEG species with end groups that are either functionalized with fluorescein or with a humanized single-chain antibody fragment (scFv) that specifically binds fluorescein.…”

8.1 Spatiotemporally Controlled Delivery of Biopharmaceuticals

“…This may be suitable for therapies that need adjustable and/or pulsative dosing, like for instance in cancer therapy or vaccination schemes [100]. While passive systems have predefined release kinetics with sustained release, stimulus sensitive systems work more like biological on/off switches.…”

“…The ability of these molecules to sense small molecules like drugs [100,104] or metabolites [105,106] in physiological relevant concentrations make them an interesting tool for stimulus sensitive DDSs. The ability of these molecules to sense small molecules like drugs [100,104] or metabolites [105,106] in physiological relevant concentrations make them an interesting tool for stimulus sensitive DDSs.…”

“…Anti-body <> antigen scFv <>FITC [100] Ligand <> receptor VEGF <> receptor domain [112] Drug <> target GyrB <> Coumermycin [104] DNA <> binding domain Operator <> Repressor [106] A good example for such a stimulus responsive polymer system is the vaccination approach developed by Gübeli et al [100]. By using a human single chain variable fragment (scFv) against a diagnostic agent (fluorescein) physical coupled to a branched eight-arm PEG as polymer backbone, an in vivo functional and biocompatible DDS was constructed.…”

“…By using a human single chain variable fragment (scFv) against a diagnostic agent (fluorescein) physical coupled to a branched eight-arm PEG as polymer backbone, an in vivo functional and biocompatible DDS was constructed. HPV16 specific IgG titers in the serum were measured by ELISA (for details also see [100]). Upon addition of the diagnostic agent fluorescein, which competitively inhibits the polymer interactions, the hydrogel dissolve, and thereby releasing its cargo (Figure 8.1.7a To form a hydrogel these components are physically coupled to a star-shaped eight-arm PEG-backbone.…”