Chitosan capped-gold nanoparticles as skin penetration enhancer for small molecules: A study in porcine skin

Skin is considered one of the most convenient sites for drug administration. The present study evaluated the effect of gold nanoparticles stabilized by chitosan (CS-AuNPs) and citrate ions (Ci-AuNPs) on skin permeation of sodium fluorescein (NaFI) and rhodamine b base (RhB) as small model hydrophilic and lipophilic permeants, respectively. CS-AuNPs and Ci-AuNPs were characterized by transmitted electron microscopy (TEM) and dynamic light scattering (DLS). Skin permeation was investigated using porcine skin with diffusion cells and confocal laser scanning microscopy (CLSM). The CS-AuNPs and Ci-AuNPs were spherical-shaped nanosized particles (38.4 ± 0.7 and 32.2 ± 0.7 nm, respectively). The zeta potential of CS-AuNPs was positive (+30.7 ± 1.2 mV) whereas that of Ci-AuNPs was negative (-60.2 ± 0.4 mV). The skin permeation study revealed that CS-AuNPs could enhance the permeation of NaFI with enhancement ratio (ER) of 38.2 ± 7.5, and the effect was superior to that of Ci-AuNPs. CLSM visualization suggested that skin permeation was enhanced by improving the delivery through the transepidermal pathway. However, the permeability of RhB, a lipophilic molecule, was not significantly affected by CS-AuNPs and Ci-AuNPs. Moreover, CS-AuNPs had no cytotoxic toward human skin fibroblast cells. Therefore, CS-AuNPs are a promising skin permeation enhancer of small polar compounds.