Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery

Abstract

Nanoparticulate pharmaceutical drug delivery systems (NDDSs) are used in research and clinical settings to overcome several issues associated with traditional drugs, such as poor aqueous solubility, low bioavailability and nonspecific distribution in the body, and to enhance drug efficiency. Multifunctional NDDSs are able to simultaneously bear a sufficient load of a drug, have increased circulation times and target the drug to the intended site of action. Moreover, they can respond to various stimuli that are characteristic of the pathological site and can even be supplemented with a contrast moiety to enable monitoring of their biodistribution, target accumulation or the efficacy of the therapy. One of the most common properties of NDDSs is the combination of prolonged circulation times with targetabilty. Active targeting of NDDSs can be achieved by surface modification of the NDDS with targeting ligands. Diseases that could benefit from NDDS-based therapy include cancer, cardiovascular diseases and infectious diseases. NDDSs that respond to different types of stimuli are an important and continuously growing area of research. This responsiveness can be used to control the properties and behaviour of NDDSs. The stimuli can be internal and intrinsic for the target site (such as changes in pH, temperature, redox condition or the activity of certain enzymes) or ones that are external and artificially applied (such as a magnetic field, ultrasound and various types of irradiation). After reaching the target, NDDSs may still need to cross the barrier of the cell membrane to deliver their drug load into the cell cytoplasm or specific organelles inside the cell; strategies to facilitate this process have been developed or are under investigation. Multifunctional NDDSs have been constructed for multimodal imaging, which could overcome several problems associated with individual imaging modalities, such as insufficient sensitivity or resolution.