Microenvironment-Activated Smart Drug Delivery System: An Integrated Review of pH-Responsive Polymers, Nanocarriers and Dual-Stimuli Innovation

The pH of the human body differs in various tissues and is more acidic in diseased conditions like tumors and inflamed tissues. These pH differences provide an opportunity to design pH responsive drug delivery systems that can selectively release drugs at the target sites. Some mechanisms initiate drug release, including polymer ionisation and swelling, chemical bond cleavage and nanocarrier destabilisation. pH-responsive systems can be categorised based on their mode of action and site of drug delivery. Among the nanocarriers that have shown great promise for improving drug stability, bioavailability and targeting efficiency are liposomes, micelles, hydrogels and nanoparticles. More sophisticated systems with pH sensitivity combined with other stimuli (e.g. temperature, enzymes) provide improved control over drug release. These smart delivery platforms have important application in cancer treatment, gastrointestinal targeting, intracellular drug delivery and inflammatory disease therapy. pH-sensitive systems for controlled and site-specific drug release enhance therapeutic efficacy and minimise side effects. Therefore, microenvironment-activated and pH-responsive drug delivery systems will be novel strategies for the future of precision medicine and targeted therapeutics.