Transdermal route has been an ever sought-after means of drug administration, regarded as being the
most convenient and patient compliant. However, skin poses a great barrier to the entry of the external particles
including bacteria, viruses, allergens, and drugs as well (mostly hydrophilic or high molecular weight drugs),
consequent to its complex structure and composition. Among the various means of enhancing drug permeation
through the skin, e.g. chemical permeation enhancers, electroporation, thermophoresis, etc. drug delivery through
nanoparticles has been of great interest. Current literature reports a vast number of nanoparticles that have been
implicated for drug delivery through the skin. However, a precise account of critical factors involved in drug
delivery and mechanisms concerning the permeation of nanoparticles through the skin is necessary. The purpose
of this review is to enumerate the factors crucial in governing the prospect of drug delivery through skin and
classify the skin permeation mechanisms of nanoparticles. Among the various mechanisms discussed are the ones
governed by principles of kinetics, osmotic gradient, adhesion, hydration, diffusion, occlusion, electrostatic interaction,
thermodynamics, etc. Among the most common factors affecting skin permeation of nanoparticles that are
discussed include size, shape, surface charge density, composition of nanoparticles, mechanical stress, pH, etc.