Controlled release

Nanotechnology

Organic chemistry

Mathematics

Mathematical analysis

Conjugate

Chemistry

Materials science

Polymer

Smart polymer

Chemical Reviews

Incorporating labile bonds inside polymer backbone and side chains yields interesting polymer materials that are responsive to change of environmental stimuli. Drugs can be conjugated to various polymers through different conjugation linkages and spacers. One of the key factors influencing the release profile of conjugated drugs is the hydrolytic stability of the conjugated linkage. Generally, the hydrolysis of acid-labile linkages, including acetal, imine, hydrazone, and to some extent β-thiopropionate, are relatively fast and the conjugated drug can be completely released in the range of several hours to a few days. The cleavage of ester linkages are usually slow, which is beneficial for continuous and prolonged release. Another key structural factor is the water solubility of polymer–drug conjugates. Generally, the release rate from highly water-soluble prodrugs is fast. In prodrugs with large hydrophobic segments, the hydrophobic drugs are usually located in the hydrophobic core of micelles and nanoparticles, which limits the access to the water, hence lowering significantly the hydrolysis rate. Finally, self-immolative polymers are also an intriguing new class of materials. New synthetic pathways are needed to overcome the fact that much of the small molecules produced upon degradation are not active molecules useful for biomedical applications.

Designing Smart Polymer Conjugates for Controlled Release of Payloads