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

Abstract

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.

Effect of crosslinking concentration on properties of 3-(trimethoxysilyl) propyl methacrylate/N-vinyl pyrrolidone gels

“…Because of the high biocompatibility and low toxicity, the utilization of hydrogels as biomaterials has recently gained great importance. Today the major fields of hydrogels applications involve: injectable polymers, ophthalmic applications, topical applications as wound and burn dressings, dental applications, drug delivery systems [ 5 ], blood compatible materials [ 6 ], implants [ 7 , 8 ], and stimuli responsive systems.…”

Polymers in Cardiology

“…These crosslinks can be broken by soluble ligand or receptor competitors, which are specific for certain diseases and can diffuse into the gel displacing the internal affinity crosslinks. Subsequently, [120,122,123], while the best studied is probably the one of Miyata et al [124][125][126][127], which is based on immunoglobulin G (IgG) antigens and corresponding antibodies grafted onto a poly(acrylamide)-(PAAm-) hydrogel, forming affinity crosslinks cleavable in the presence of free antigen. In an own study, we provided a thorough in vitro characterization of PAAm-hydrogels regarding drug permeability with the purpose of exploring the applicability of such hydrogels for implant-associated LDD systems [128].…”

Kinetics, Equilibrium, and Thermodynamics for Conjugation of Chitosan with Insulin-Mimetic [meso-Tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4−) in an Aqueous Solution

“…Intensive research is being conducted to develop polymer-based therapeutic systems. , Polymer conjugation increases the therapeutics’ stability and efficacy . In the formulation of therapeutic agents, various polymers such as poly­[ N -(2-hydroxy-propyl)­methacrylamide], polyacrylamide, poly­(vinyl alcohol), poly­(γ-glutamic acid), and chitosan have been utilized as carriers.…”