Controlled release intends to deliver the therapeutic compound in the chosen region and in the required period. Both the release rate and where it takes place can be controlled.
- Release rate: Different parameters must be adjusted, the composition being the main one. The release could be systematically or locally, and the rate could be very fast, being able to release all the encapsulated compound in a few minutes or, conversely, very low, taking place a sustained release over time for several weeks.
- Stimuli-responsive systems: Stimuli-responsive systems are able to control drug biodistribution in response to specific stimuli, either those found in the local environment of the target place (changes in pH, enzyme concentration or redox gradients) and those that are triggered by an external physical stimulus such as heat, ultrasound or light.
- High circulation times
- Enhancement of permeability and retention effects
- Reduction of side effects
- Release at the therapeutic target
- pH sensitive: Acidification of the nanocarrier environment triggers the release of its contents. It has been shown to be a great technique to target cancer cells since they have lower pH values than normal. Additionally, it can specifically reach organelles inside the cell like endosomes or lysosomes which pH is more acidic.
- Enzyme-responsive: The destabilization of the nanocapsule membrane in the presence of a certain enzyme therefore releasing the cargo helps in accurately drug delivery. Enzymes that are overexpressed in the target tissue are great triggers for enzyme-responsive nanocarriers. Some examples could be phospholipase, matrix metalloproteinases, urokinase plasminogen activator, and many others that are involved in inflammatory and cardiovascular diseases as well as different cancers.
- Redox responsive: The higher concentration inside cancer cells of glutathione generates a redox gradient that can be used to trigger the release of pharmaceuticals in its destiny.
- Thermal sensitive liposomes: This strategy is especially useful when drug delivery is used in combination with local hyperthermia for cancer treatments. This way, when the heat treatment starts, the pharmaceutical is released which results in superior targeting and treatment efficiency.