The use of colloidal particles as drug delivery carriers holds a great promise in terms of improvement
of traditional treatment and diagnosis of human diseases. Nano- and microsized particles of a
different composition including organic and inorganic materials can be fabricated with a great control
over size, shape and surface properties. Nevertheless, only some few formulations have surpassed the
benchtop and reached the bedside. The principal obstacle of colloidal drug delivery systems is their poor
accumulation in target tissues, organs and cells, mainly by efficient sequestration and elimination by the
mononuclear phagocytic system. Recent evidence suggests that, besides size, the surface character of
colloidal systems is the most determinant design parameter that may ultimately guarantee successful
biological performance. To approach these issues, materials designers and engineers can make use of
multiple strategies and tools to finely modulate the particles’ surface towards highly efficient and biocompatible
materials. In this article, we provide an overview of the most relevant colloidal drug delivery
systems, a summary of the available literature regarding the effects of surface charge, hydrophobicity
and softness on biological response, and finally, we review the key points of surface modification strategies
with organic, inorganic and biological materials.
