Article

Drug-sensing hydrogels for the inducible release of biopharmaceuticals.

Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland.
Nature Material (impact factor: 32.84). 09/2008; 7(10):800-4. DOI:10.1038/nmat2250 pp.800-4
Source: PubMed

ABSTRACT Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF(121) for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

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Keywords

aminocoumarin antibiotic coumermycin
 
antibiotic-sensing hydrogel
 
bacterial gyrase subunit B
 
cellular receptors
 
clinically validated novobiocin
 
drugs
 
entrapped protein pharmaceutical VEGF(121)
 
GyrB subunits
 
human umbilical vein endothelial cells
 
human vascular endothelial growth factor
 
hydrogel formation
 
materials science
 
novel design concepts
 
potent pharmacologic mode
 
protein-protein interactions
 
regulating cell fate
 
smart devices
 
stimuli-sensing materials
 
stimuli-sensing smart hydrogels
 
time-dependent liberation