A review of drug release mechanisms from nanocarrier systems

•Recent progress of using nanocarrier systems for drug delivery are discussed.•Controlled drug release through different linker cleavages are summarized.•Insights on the drug release mechanism and factors are also provided.

The most common methods used for drug administrations are pills, injections, lotions and suppositories. The preferred means is oral dosage forms as it is simple, painless and self-administered. However, the drugs are usually degraded within gastrointestinal tract or not absorbed in sufficient quality to be effective. Over the years, a variety of other administration means have evolved to show specific advantages for particular agents and certain diseases. In this review, various nano-delivery systems consisting of different covalent linkages to conjugate the therapeutic molecules as well as those that carry the unmodified drug molecules by encapsulating or complexation are summarized, including ester, amide/peptide, disulfide, hydrazone, hypoxia-activated and self-immolative linkages. The mechanisms for controlled drug release are also discussed. In addition, the new mechanism of the recently developed photochemistry or thermolysis to trigger controlled drug release and the applications are also covered.