Tuning the Surface Chemistry of Melanin-Mimetic Polydopamine Nanoparticles Drastically Enhances Their Accumulation into Excised Human Skin

Melanin-mimetic polydopamine nanoparticles (PDA NPs) are emerging as promising candidates for topical and transdermal drug delivery because they mimic melanin, a naturally occurring skin pigment. However, our knowledge of their interactions with human skin remains limited. Hence, we set out to investigate the role of PDA NP surface chemistry in modulating their skin deposition. PDA NPs were synthesized by base-catalyzed oxidative self-polymerization of dopamine and functionalized with poly(ethylene glycol) (PEG) bearing different termini to obtain neutral, anionic, cationic, and hydrophobic PEGylated NPs. NPs were characterized by dynamic light scattering, transmission electron microscopy, Fourier transform-infrared spectroscopy, and X-ray photoelectron spectroscopy. The NPs were then labeled with rhodamine B, and their skin interactions were investigated both in vitro, using a Strat-M membrane, and ex vivo, using excised whole thickness human skin. In vitro diffusion studies revealed that the NPs did not permeate transdermally, rather the NPs accumulated in the Strat-M membrane after 24 h of incubation. Membrane deposition of the NPs showed a strong dependence on surface chemistry, with anionic (unmodified and carboxyl-terminated PEGylated) NPs achieving the highest accumulation, followed by neutral and cationic NPs, whereas hydrophobic NPs achieved the lowest degree of accumulation. In ex vivo permeation studies, we observed that surface modification of PDA NPs with PEG serving as an antifouling coating is essential to maintaining colloidal stability upon skin contact. Moreover, anionic PEGylated NPs were able to achieve 78% skin accumulation, which was significantly higher than neutral and cationic NPs (51 and 34% accumulation, respectively). Our findings provide important insights into the role of surface chemistry in enhancing the skin accumulation of melanin-mimetic PDA NPs as potential sunscreens and carriers for skin-targeted treatments.