Sunoqrot Suhair, Mahmoud Nouf N, Ibrahim Lina Hassan, Al-Dabash Saba'a, Raschke Hannes, Hergenröder Roland
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund 44139, Germany.
ACS Biomater Sci Eng. 2020 Aug 10;6(8):4424-4432. doi: 10.1021/acsbiomaterials.0c00196. Epub 2020 Jul 16.
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.
黑色素模拟聚多巴胺纳米颗粒（PDA NPs）作为局部和透皮给药的有前景的候选物正在兴起，因为它们模拟了黑色素，一种天然存在的皮肤色素。然而，我们对它们与人体皮肤相互作用的了解仍然有限。因此，我们着手研究PDA NP表面化学在调节其皮肤沉积中的作用。通过多巴胺的碱催化氧化自聚合合成PDA NPs，并用带有不同末端的聚乙二醇（PEG）进行功能化，以获得中性、阴离子、阳离子和疏水PEG化的纳米颗粒。通过动态光散射、透射电子显微镜、傅里叶变换红外光谱和X射线光电子能谱对纳米颗粒进行表征。然后用罗丹明B标记纳米颗粒，并使用Strat-M膜在体外以及使用切除的全层人体皮肤在离体条件下研究它们与皮肤的相互作用。体外扩散研究表明，纳米颗粒不会经皮渗透，而是在孵育24小时后在Strat-M膜中积累。纳米颗粒在膜上的沉积显示出对表面化学的强烈依赖性，阴离子（未修饰和羧基末端PEG化）纳米颗粒的积累最高，其次是中性和阳离子纳米颗粒，而疏水纳米颗粒的积累程度最低。在离体渗透研究中，我们观察到用PEG作为防污涂层对PDA NPs进行表面修饰对于在皮肤接触时保持胶体稳定性至关重要。此外，阴离子PEG化纳米颗粒能够实现78%的皮肤积累，这显著高于中性和阳离子纳米颗粒（分别为51%和34%的积累）。我们的研究结果为表面化学在增强黑色素模拟PDA NPs作为潜在防晒霜和皮肤靶向治疗载体的皮肤积累中的作用提供了重要见解。
