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 dy-namic 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.