pH‐responsive polymers for drug delivery: Trends and opportunities

Abstract

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.

Dynamic Modeling for Synthesis of Tailored Microgels with Charged Domains

“…For the pK a value of polymerized MAA, a value of 4.8 was reported by Singh and Nayak. 13 Buback et al 52 explain the difference in pK a value of the polymerized MAA due to the "exchange of hydrogen cations as well as counterions during polymerization". For the kinetic model of the NIPAM−BIS− MAA synthesis in this work, we consider the change in pK a as negligible as the resulting model is insensitive to changes in the pK a parameter values.…”

“…Previously, it was found that the p K a value changes during the polymerization of MAA. For the p K a value of polymerized MAA, a value of 4.8 was reported by Singh and Nayak . Buback et al explain the difference in p K a value of the polymerized MAA due to the “exchange of hydrogen cations as well as counterions during polymerization”.…”

“…These networks display a fully reversible volume change in response to a threshold in external stimuli-like temperature, pH, or ionic strength of their environment . Microgels based on poly­( N -isopropylacrylamide) (PNIPAM) are one of the most studied thermoresponsive microgels due to their volume phase transition temperature in aqueous solution of around 32 °C being close to physiological temperature. − By adding functional groups such as carboxylic acids to thermoresponsive microgels, these microgels are also attributed pH responsiveness. − Microgels with such dual stimulus swelling response find applications in drug delivery, − catalysis, , sensing, and membranes . Tan and Tam present a detailed review of pH-responsive microgel research.…”

Advanced hybrid silica nanoparticles with pH-responsive diblock copolymer brushes: optimized design for controlled doxorubicin loading and release in cancer therapy

“…pH-Responsive polymers possess the unique ability to undergo conformational changes or alterations in hydrophilicity in response to local pH conditions. 20,21 This characteristic is harnessed to prevent premature drug release, taking advantage of the pH disparity between healthy and cancerous tissues. 22,23 In our previous investigations, we successfully synthesized MSNs coated with poly(2-(diethylamino)ethyl methacrylate) as pore caps, enabling the loading of DOX.…”

Flavylium-Containing Stimuli-Responsive RAFT Polymers: Synthesis and Enhanced Stability

“…Intelligent/responsive polymers have attracted a significant surge of attention over the past few decades due to their capability to respond to single or multiple chemical and/or physical stimuli, and a great deal of research has been devoted to creating environmentally responsive large molecules that can be transformed into innovative smart materials. , These materials have found extensive applications in fields like controlled drug release, artificial muscles, and medical devices and biosensors . More recently, multiresponsive polymers have gained popularity due to their multidimensional responses, which improve their sensitivity and specificity .…”