**3. Nanomedicines pharmacokinetic and regulations**

The pharmacokinetic parameters of nanomedicines are similar to free drugs with addition phase after drug administration, which is the liberation phase beside the standard absorption, distribution, metabolism, and excretion (ADME). This new phase is controlled by particle nature, size, shape, and surface properties. It is worth to mention that particle size is very important for absorption and elimination. Particles with particle size <5 nm is easily excreted from the kidney, while larger particle size could be eliminated by the liver or engulfed by mononuclear-phagocyte system. Moreover, particle size and shape can affect particle accumulation in targeted tissues like ellipsoidal shape that has better distribution and retention in tumor tissue than spherical one. Surface modification of nanoparticles can affect particle uptake and elimination. Many nanoparticles are coated for active and passive targeting. Passive targeting is a non-specific retention in target tissue like solid cancer tissue by enhanced permeability and retention mechanism. Active targeting is the selective uptake of nanomedicine by specific cells. Target moieties could be protein, antibody, or small molecule selective to specific tissues or cells. This mechanism is mainly controlled by homing to overexpressed cell surface receptors.

The Food and Drug Administration classified nanoscale materials to nanomaterials as "materials used in the manufacture of nanomedicine" or nanomedicine as "final products," The FDA approved 51 nanomedicines by the year 2016, 40% of which were in clinical trials between 2014 and 2016. According to the FDA evaluation of nanomedicines, it includes the physicochemical properties, followed by pharmacokinetics evaluation of nanomedicines. The pharmacokinetics evaluation includes (1) rate and amount of absorption, (2) retention in circulation, (3) half-life and complete elimination, (4) bioavailability differences, (5) distribution or accumulation to the body or specific tissue for active targeting, (6) decomposition or metabolism, (7) elimination, and (8) toxicity assessment of nanomedicines. On the other hand, the European Medicines Agency defined nanomedicines as "drugs composed of nanomaterials 1–100 nm in size, and these are classified into liposomes, nanoparticles, magnetic nanoparticles, gold NPs, quantum dots, dendrimers, polymeric micelles, viral and non-viral vectors, carbon nanotubes, and fullerenes." EMA has approved eight commercially available nanomedicines as first-generation nanomedicines. Currently, there are 48 nanomedicines in clinical trials (Phases 1–3) in the EU. EMA evaluates the pharmacokinetics and pharmacodynamics of nanomedicines through investigation of their chemical composition and physicochemical properties [8].
