Multiresponsive hydrogels, which are smart soft materials that respond to more than one external stimulus, have emerged as powerful tools for biomedical applications, such as drug delivery. Within this context and with the aim of eliminating the systematic administration of antibiotics, special attention is being paid to the development of systems for controlled delivery of antibiotic for topical treatment of bacterial infections. In this work, an electro-chemo responsive hydrogel able to release chloramphenicol (CAM), a broad spectrum antibiotic also used for anticancer therapy, is proposed. This has been prepared by grafting poly(acrylic acid) (PAA) to sodium alginate (Alg) and in situ encapsulation of poly(3,4-ethylenedioxythiophene) nanoparticles loaded with CAM (PEDOT/CAM NPs), which were obtained by emulsion polymerization. Although the response to electrical stimuli of PEDOT was the main control for the release of CAM from PEDOT/ CAM NPs, the release by passive diffusion had a relatively important contribution. Conversely, the passive release of antibiotic from the whole engineered hydrogel system, Alg-g-PAA/PEDOT/CAM, was negligible, whereas significant release was achieved under electrostimulation in an acid environment. Bacterial tests and assays with cancer cells demonstrated that the biological activity of CAM remained after release by electrical stimulation. Notably, the successful dual-response of the developed hydrogel to electrical stimuli and pH changes evidence the great prospect of this smart material in the biomedical field, as a tool to fight against bacterial infections and to provide local cancer treatment.

Active pharmaceutical ingredients (API) are synthesized using highly reactive reagents, catalysts, and solvents. Some of those persist as impurities in the final product and are genotoxic or carcinogenic. The conventional processes used for API purification and isolation are able to achieve the limits imposed by regulatory agencies, but at the expense of significant API losses. Here we report the development of a model to aid in the decision of which dedicated purification process, membrane or adsorption, is most suitable for removal of genotoxic impurities (GTIs), according with a small set of key intrinsic parameters. A hybrid process was developed, combining these two unit operations, to be applied when the use of OSN or adsorption alone result on non-acceptable API losses. Membrane solute rejection and solvent flux was used as parameter for OSN. In the case of adsorption, two isotherm models, Langmuir and Freundlich, were considered. The effect of the recirculation stream and amount of adsorber used on the hybrid process was investigated. Case studies were experimentally validated, confirming that combining the two unit operations can reduce API loss from 24.76% in OSN to 9.76% in a hybrid process. Economic and environmental analyses were performed.