pH‐responsive polymers for drug delivery: Trends and opportunities

Polymer science has applications in biomedical engineering, prosthetics, surgical implants, and prospective pharmaceutical excipients for drug delivery. “Intelligent or Smart Polymers” are created for drug targeting either by derivatization of natural polymers or controlled radical polymerization of electrolytes. Their mode of action is governed by the environmental stimuli viz. temperature, pH, ionic concentration, magnetism, and so on. pH-responsive polymers, because of their self-assembling behavior, alter their solubility, conformation, surface activity, and hydrophilicity when exposed to a specific pH. The physiological pH varies from acidic nuclei to alkaline cytoplasm and highly acidic gastric juice to slightly alkaline plasma; thus, various polymers are under study for delivering small molecules, genes, peptides, enzymes, growth factors, and antibodies. The non-invasive drug delivery routes like oral, ocular, nasal, pulmonary, transdermal, and rectal routes can be explored for targeting recombinant proteins, monoclonal antibodies, and small molecules with particular emphasis on the individual's physiological and pathological state. Further, these polymers can be designed into various architectures like dendrimers, liposomes, micelles, and metallic nanoparticles that can serve as drug reservoirs for sustaining drug release. The challenges in this field are the selection of biocompatible polymers with ease of synthesis and scale-up, ensuring effective drug-loading, and stability aspects, producing robust pharmacological data, and timely regulatory approvals. This review exclusively explores the physicochemical characteristics of pH-responsive polymers, their categorization, various architectural entities, recent studies and patents, and their emerging applications concerning specific diseases.