For topically applied nanoparticles a frequently discussed question is if and to which extent the nanoparticles might penetrate deeply into the epidermis,
maybe reaching dermis and finally the systemic circulation.
At present there is an increased concern that very small nanoparticles might penetrate via the hydrophilic channels
(about 50nm sized) into the skin.
This is especially valid for example for titanium dioxide nanoparticles used in sunscreens which have sizes about 10–20 nm. Of course the quantity will be definitely very low but the titanium dioxide nanoparticles are not biodegradable.
In addition even lowparticle quantities can interact with the immune system.
Regarding this one will be on the safe side with lipid nanoparticles because typically the size is around 200 nm and therefore well above the 50 nm.
Even if smaller lipid nanoparticles should be present in the formulation, the material can be biodegraded.
In addition the theoretical potential amounts in the skin are so low that they are few dimensions below the concentrations
which caused an effect on cytokine production and release.
Even assuming that some lipid nanoparticles might arrive in the systemic blood circulation, they will be very well tolerated.
Based on their composition they are rather a kind of parenteral nutrition.
In the 1990s in vivo studies showed that intravenously injected lipid nanoparticle suspensionswere verywell tolerated (Weyhers, 1995; Weyhers et al., 1995).