In vitro characterization of polyacrylamide hydrogels for application as implant coating for stimulus-responsive local drug delivery.

The improvement of well-established local drug delivery (LDD) systems, often providing drug release independently of their need, is a challenge of current implant technology. Systems that sense signals caused by a certain disease, judge the magnitude of the signal and act to release the right amount of drug in response are hence searched for. Specific responsive hydrogels with antibody-antigen cross-links, whose non-covalent interaction is broken in the presence of the corresponding antigen and reclosed in its absence, are a promising candidate. However, the challenging implementation of such antigen-responsive hydrogels as implant coating and their applicability for implant-associated LDD systems have not been explored so far. In this context and in order to define adequate gel properties for the envisaged application, we prepared a matrix at examples of polyacrylamide hydrogels of different gel architectures, gel contents and cross-linking degrees and investigated their impact on the permeation of the differently sized model proteins bovine serum albumin (BSA), protein A and myoglobin in a specifically designed chamber simulating an implant-associated LDD system and the mechanical stability of the polymeric network. Water uptake, as estimated by Karl Fischer titration, which was mainly influenced by gel content, seems to primarily govern drug permeability and mechanical stability. Within the investigated matrix, a medium gel content of 15.0 w% acrylamide and N,N′-methylenebisacrylamide evidenced low drug permeability, enough tensile strength and flexibility for integration of antibody-antigen cross-links, which we could successfully evidence via fluorescence microscopy. A stimulus-triggered release of BSA through such a hydrogel could be moreover demonstrated. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]