Physically cross-linked pH-responsive hydrogels with tunable formulations for controlled drug delivery

A variety of pH responsive hydrogels possessing macroporous interiors resembling a honey-comb framework with a continuous skin on the surface have been developed by free radical aqueous copolymerization of acrylic acid (AAc) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) (poly(AAc-co-DMAEMA) (PAD) hydrogels). This one step polymerization process makes scaling-up easier for mass production. Our formulations, being devoid of any chemical cross-linkers, remained dimensionally stable in buffer solutions of pH 1.2–7.4 with interlocked nanogels being identified as the building blocks of the network structures. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), uniaxial compression testing and scanning electron microscopy (SEM) were used to characterize the hydrogels (PADs). Compressive elastic modulus and compressive strength of the swollen hydrogels at pH 7 were found to vary with composition from ∼3 to ∼11 kPa and ∼178 to ∼206 kPa, respectively. The swollen gels showed fairly strong viscoelastic behaviour and underwent deformation from ∼70% to 85% before failure, indicating the formation of robust 3D structures of PADs. Preliminary investigation into the biocompatibility of our hydrogels done by cytotoxicity assays using HeLa and McCoy mouse fibroblast cell lines have revealed that they are non-cytotoxic, paving the way for further biomedical applications. Swelling behaviour and release kinetics of bovine serum albumin (BSA) were investigated in various buffer solutions that mimic the pH-metric hierarchy in the gastrointestinal (GI) tract. Equilibrium swelling ratio was found to vary from 171% (mass) to 2027% (mass) depending on the pH and composition of hydrogels. Different compositions of PAD systems were investigated to verify the possibility of tailor-making the drug release behaviour of PAD formations.