So size does matter. However, its distribution is just as important as size. The reason is that the size of the particles at the end of the production process is not uniform, but has a distribution. In this population of particles, those with the right size can target the desired tissue, while the others may miss it or hit outside the target area, leading to the infamous side effects (see Figure for an illustration of the concept of PDI). Consequently, size distribution is a factor that influences therapeutic efficacy in conjunction with the magnitude of side effects. In addition, recent studies have shown that it also influences the pathway of cellular uptake of CSHNs by controlling in vitro and in vivo behaviour, particularly particle adhesion, interactions with the cell membrane, and their penetration ability through physiological drug barriers . For this reason, the degree of size distribution is currently used as a measure of the efficiency and stability of drug delivery systems. Terminologically, this parameter is expressed by the polydispersity index (PDI). This is a unitless term referred to as the lognormal distribution width of the particle diameter. Its value ranges from 0.0 (perfectly uniform size) to 1.0 (broad distribution of particle size). The cut-off value is 0.2: any PDI smaller than this value is considered to be a homogeneous distribution of particle size (in other words, monodispersity) . However, in some articles, this value is reported as 0.3. More specific standards should therefore be established.