Impact of semi-solid formulations on skin penetration of iron oxide nanoparticles

Background: This work aimed to provide useful information on the incidence of the choice of formulation in semi-solid preparations of iron-oxide nanoparticles (IONs). The appropriate analytical methods to assess the IONs physical stability and the effect of the semi-solid preparations on IONs human skin penetration were discussed. The physical stability of IONs (Dh = 31 ± 4 nm; ζ = -65 ± 5 mV) loaded in five semi-solid preparations (0.3% w/v), namely Carbopol gel (CP), hydroxyethyl cellulose gel (HEC), carboxymethylcellulose gel (CMC), cetomacrogol cream (Cet) and cold cream was assessed by combining DLS and low-field pulsed NMR data. The in vitro penetration of IONs was studied using human epidermis or isolated stratum corneum (SC). Results: Reversible and irreversible IONs aggregates were evidenced only in HEC and CMC, respectively. IONs diffused massively through SC preferentially by an intercellular pathway, as assessed by transmission electron microscopy. The semi-solid preparations differently influenced the IONs penetration as compared to the aqueous suspension. Cet cream allowed the highest permeation and the lowest retained amount, while cold cream and CP favored the accumulation into the skin membrane. Conclusion: Basic cutaneous semi-solid preparations could be used to administer IONs without affecting their permeation profile if they maintained their physical stability over time. This property is better discriminated by low-field pulsed NMR measurements than the commonly used DLS measurements.