Hydrogels have been used variously as agents for delivering proteins, drugs, antibodies, DNA, growth factors and immunological molecules to various tissues for a range of biomedical research applications. It is their ability to swell depending on external factors, their inherent biocompatibility, biodegradability, non-toxicity and mechanical stability that make them important.
Now, researchers at CSIR-CLRI Adyar, in Chennai, Tamil Nadu, India, have demonstrated how reduction followed by oxidative refolding can convert natural albumin found in serum into a hydrogel that responds to stimuli, such as changing redox conditions without the use of toxic glutaraldehyde as a cross-linker, a problem facing earlier efforts to make hydrogels from albumin and other biomaterials. They tried hydrogel formation at 75, 150, 300, 450, 600 and 750 micromolar concentrations across a pH range from 2.0 to 10.0 and demonstrated that 150 micromolar is the baseline although 450 micromolar is optimal while a pH between 4.5 and 8.0 is needed. Hydrogel swelling is maximal at a pH above 9.0.
Serum albumin is the most abundant globular protein in blood, the team explains, consisting of 580 amino acid residues with 17 disulfide bridges; its natural role is as a transport protein in the blood for numerous endogenous and exogenous compounds. The team points out that their serum hydrogel is more responsive to redox conditions than pH changes, a property that has not been widely studied in previous hydrogels.
Such a responsive hydrogel from an autogenic substance derived from the patient's own tissues could make the material even more biocompatible than polymer hydrogels and the team has already demonstrated proof of principle in the laboratory of the material, albeit one derived from the more readily available bovine serum albumin, BSA. They demonstrated body temperature controlled release of the broad-spectrum, polyketide antibiotic tetracycline, as a model drug from the hydrogel. The intracellular environment is predominantly in the reduced state and so this hydrogel is perfectly suited for such delivery. [Gnanamani et al, Sci Rep, 2015, 5, online; DOI: 10.1038/srep15977]
The team points out that the chemistry of their serum albumin hydrogel and the relatively simple and additive free preparative steps points the way to designing strategies for making scaffolds, microspheres and nanoparticles from this and related materials. "Natural materials are biocompatible and biodegradable compared to synthetic polymeric materials. Proteins, a natural material, can be effectively used due to their availability and unique structural properties," the team reports in the journal Scientific Reports.
"Our next step is on stimuli responsive nanoparticles as a carrier material to deliver drugs under a reduced environment, that is to target cancer cells," Gnanamani told Materials Today.
David Bradley blogs at Sciencebase Science Blog and tweets @sciencebase, he is author of the bestselling science book "Deceived Wisdom".