The extent to which topically applied solid nanoparticles can penetrate the stratum corneum and access the underlying viable epidermis and the rest of the body is a great potential safety concern. Therefore, human epidermal penetration of a novel, transparent, nanoparticulate zinc oxide sunscreen formulation was determined using Franz-type diffusion cells, 24-hour exposure and an electron microscopy to verify the location of nanoparticles in exposed membranes. Less than 0.03% of the applied zinc content penetrated the epidermis (not significantly more than the zinc detected in receptor phase following application of a placebo formulation). No particles could be detected in the lower stratum corneum or viable epidermis by electron microscopy, suggesting that minimal nanoparticle penetration occurs through the human epidermis.

One of the most important determinants of dermatological and systemic penetration after topical application is the delivery or flux of solutes into or through the skin. The maximum dose of solute able to be delivered over a given period of time and area of application is defined by its maximum flux (J(max), mol per cm(2) per h) from a given vehicle. In this work, J(max) values from aqueous solution across human skin were acquired or estimated from experimental data and correlated with solute physicochemical properties. Whereas epidermal permeability coefficients (k(p)) are optimally correlated to solute octanol-water partition coefficient (K(ow)) and molecular weight (MW) was found to be the dominant determinant of J(max) for this literature data set: log J(max)=-3.90-0.0190MW (n=87, r(2)=0.847, p<0.001). Estimated solubility in octanol (S(oc)) was also a determinant, but improvement in the regression by the addition of log S(oc) was small (r(2) increased to 0.856). Addition of other physicochemical parameters to MW by forward stepwise regression only marginally improved the regression with a melting point (Mpt) term (r(2)=0.879) and then hydrogen bonding acceptor capability (H(a)) (r(2)=0.917) is significant. Validation of the equation above was carried with a number of other data sets: an aqueous vehicle with full- and split-thickness skin (r(2)=0.784, n=56), some pure solutes (r(2)=0.537, n=34), an aqueous vehicle with ionizable solutes (r(2)=0.282, n=54) and solutes from a propylene glycol vehicle (r(2)=0.484, n=36). An analysis of the entire database gave the equation log J(max)=-4.52-0.0141MW (n=278, r(2)=0.688, p<0.001), with inclusion of Mpt and H(a) increasing r(2) to 0.760 (n=269). Separate analysis of full- and split-thickness skin data confirmed that the dermal resistance term had only a marginal effect on overall J(max). Application of the latter model to an in vivo situation where the dermal capillary bed is slightly below the epidermal-dermal junction revealed that the dermal resistance term was unnecessary for in vivo predictions for most solutes.

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