Stimuli-Responsive Drug Delivery Systems Based on Amphiphilic Polymers

Stimuli-responsive drug delivery systems harness the unique properties of amphiphilic polymers—macromolecules bearing both hydrophobic and hydrophilic segments—to self-assemble into nanoscale carriers such as micelles, vesicles and unimolecular constructs. In aqueous environments, these architectures encapsulate therapeutic agents within their hydrophobic cores or interstitial domains, protecting payloads from premature degradation and minimising off‐target effects. Upon exposure to specific internal cues (for example pH variations, redox gradients, enzyme activity or temperature shifts) or external triggers (such as light or magnetic fields), conformational changes or bond cleavages in the polymer backbone induce controlled disassembly or pore formation, effecting on‐demand release of the drug. This dynamic responsiveness enables site‐specific delivery, enhanced cellular uptake and reduced systemic toxicity. Advances in polymer design—ranging from hyperbranched and brush‐on‐brush topologies to dendritic and cyclic architectures—have broadened the scope of stimuli sensitivity and fine‐tuned release kinetics. Such platforms are driving progress in precision medicine for applications in oncology, inflammation, infectious disease and beyond, while presenting challenges in large‐scale manufacture, in vivo stability and regulatory translation.

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Stimuli-Responsive Drug Delivery Systems Based on Amphiphilic Polymers publication trend

The graph below shows the total number of articles in stimuli-responsive drug delivery systems based on amphiphilic polymers across all publications each year (not limited to Nature Index journals).

Technical terms

Amphiphilic polymer: A macromolecule containing both hydrophilic (water‐attracting) and hydrophobic (water‐repellent) segments that can self‐assemble in aqueous media.

Micelle: A nanoscale aggregate formed by amphiphilic molecules arranging hydrophobic regions inward and hydrophilic regions outward.

Stimuli-responsive: Characteristic of a material to undergo physicochemical changes upon exposure to defined internal or external triggers.

Hyperbranched polymer: A highly branched macromolecule with a three‐dimensional architecture offering multiple functional end groups.

Bottlebrush copolymer: A polymer comprising a linear backbone densely grafted with side chains, resembling a bottlebrush, often enhancing stability and functional density.

References

1. Tumor microenvironment-responsive hyperbranched polymers for controlled drug delivery. Journal of Pharmaceutical Analysis (2024).
2. Construction of Enzyme-Responsive Micelles Based on Theranostic Zwitterionic Conjugated Bottlebrush Copolymers with Brush-on-Brush Architecture for Cell Imaging and Anticancer Drug Delivery. Molecules (2022).