Designed Monomers and Polymers

pH and Thermo-Responsive Polymer Architectures from Designed Monomers for Controlled Drug Release Applications

The design and synthesis of stimuli-responsive polymers have emerged as a transformative frontier in drug delivery science, offering unprecedented control over therapeutic agent release profiles. Among various stimuli, pH and temperature represent the most physiologically relevant triggers, as both parameters exhibit characteristic variations across healthy and diseased tissues, tumor microenvironments, inflammatory sites, and intracellular compartments. Rational monomer design plays a pivotal role in engineering polymer architectures with precisely tunable response thresholds, release kinetics, and biocompatibility profiles essential for clinical translation. pH-responsive polymer systems exploit ionizable functional groups such as carboxylic acids, amines, and sulfonamides that undergo protonation or deprotonation in response to local pH changes, inducing conformational transitions and controlled payload release. Thermo-responsive polymers, particularly those exhibiting lower critical solution temperature behavior, undergo reversible hydrophilic-to-hydrophobic transitions near physiological temperatures, enabling on-demand drug release with minimal systemic toxicity. The integration of both pH and thermo-responsive functionalities within a single polymer architecture creates dual-stimuli systems capable of achieving highly selective, site-specific drug delivery with enhanced therapeutic efficacy.

Recent advances in controlled radical polymerization techniques, including RAFT, ATRP, and ring-opening polymerization, have enabled precise synthesis of block copolymers, grafted architectures, and crosslinked hydrogel networks with well-defined molecular weights and narrow dispersity. These developments, combined with emerging computational design strategies and machine learning-guided monomer screening, are accelerating the discovery of next-generation responsive polymer platforms. This special issue invites original research articles, comprehensive reviews, and short communications addressing the rational design, synthesis, characterization, and application of pH and thermo-responsive polymer systems from functional monomers. Contributions spanning fundamental polymer chemistry, nanoparticle formulation, hydrogel engineering, and preclinical drug delivery evaluation are strongly encouraged. Interdisciplinary submissions bridging polymer science, pharmaceutical technology, biomaterials engineering, and computational chemistry are particularly welcome. Potential topics included, but not limited,

• Rational design of pH-responsive monomers bearing ionizable functional groups for tumor microenvironment-triggered anticancer drug release
• LCST-tunable thermo-responsive polymer nanoparticles from designed N-isopropylacrylamide derivatives for on-demand chemotherapy delivery
• Dual pH and thermo-responsive block copolymer architectures synthesized via RAFT polymerization for intracellular drug delivery
• Injectable thermo-responsive hydrogels from functional monomers for localized and sustained post-surgical drug release
• pH-responsive polyelectrolyte multilayer nanocapsules from designed monomers for gastrointestinal drug delivery applications
• Stimuli-responsive polymer prodrug conjugates from acid-labile monomers: synthesis, stability and controlled release performance
• Computational and machine learning-guided design of pH and thermo-responsive monomers for optimized drug release kinetics
• Biocompatibility and cytotoxicity evaluation of dual-stimuli responsive polymer nanocarriers from designed functional monomers
• pH and temperature co-responsive microgel systems from crosslinked functional monomers for multiplexed therapeutic delivery
• 3D-printable pH and thermo-responsive hydrogel scaffolds from designed monomers for personalized drug delivery and tissue engineering