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

Abstract

A variety of pH responsive hydrogels possessing macroporous interiors resembling honey-comb framework with 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 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.

Tunable temperature‐ and shear‐responsive hydrogels based on poly(alkyl glycidyl ether)s

“…These hydrophilic networks are bound by chemical or physical crosslinks between the molecules . Stimuli‐responsive hydrogels belong to a unique class of materials that adapt to environmental cues such as pH, temperature, light and mechanical impetus . Temperature and shear stress are examples of two important stimuli responses that enable effective drug delivery, additive manufacturing and tissue engineering .…”

Adsorption and protonation of peptides and proteins in pH responsive gels

“…Release occurs due to diffusion through the swollen network since the drug is only physically entrapped inside the hydrogel. For example, pH-responsive hydrogels have been considered for potential applications in the controlled oral delivery of several proteins including, among many others, insulin (Brøndsted and Kopeček 1991, Lowman et al 1999, Nakamura et al 2004, Yamagata et al 2006, calcitonin (Torres-Lugo and , Kim et al 2003, lysozyme (van de Weert et al 2000a, Hoven et al 2007, Shi et al 2008, Zhang et al 2008, amylase (Liang-chang et al 1992), bovine serum albumin (BSA) (Zhang et al 2011, Gao et al 2012, Suhag et al 2015, human growth hormone and interferon-β (Kamei et al 2009). In addition, pH-sensitive hydrogels can be used for delivery of therapeutics to specific tissue, which has not only been considered in basic research but also in clinical trials (Cabral and Kataoka 2014).…”

Hybrid cross‐linked hydrogels as a technology platform forinvitrorelease of cephradine

“…It means water absorption in polymer chains occupies the free volume spaces between polymer chains. With increase in time, volume fraction of water increased, but the volume fraction of free spaces decreased …”