Kim Hye Ji, Oh Seaung Youl
College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
Biomol Ther (Seoul). 2018 Mar 1;26(2):182-190. doi: 10.4062/biomolther.2017.203.
The objective of this work is to evaluate the effect of polyamidoamine (PAMAM) dendrimers on electroosmotic flow (EOF) through skin. The effect of size and concentration of dendrimer was studied, using generation 1, 4 and 7 dendrimer (G1, G4 and G7, respectively). As a marker molecule for the direction and magnitude of EOF, a neutral molecule, acetoaminophen (AAP) was used. The visualization of dendrimer permeation into the current conducting pore (CCP) of skin was made using G4-fluorescein isothiocyanate (FITC) conjugate and confocal microscopy. Without dendrimer, anodal flux of AAP was much higher than cathodal or passive flux. When G1 dendrimer was added, anodal flux decreased, presumably due to the decrease in EOF by the association of G1 dendrimer with net negative charge in CCP. As the generation increased, larger decrease in anodal flux was observed, and the direction of EOF was reversed. Small amount of methanol used for the preparation of dendrimer solution also contributed to the decrease in anodal flux of AAP. Cross-sectional view perpendicular to the skin surface by confocal laser scanning microscope (CLSM) study showed that G4 dendrimer-FITC conjugate (G4-FITC) can penetrate into the viable epidermis and dermis under anodal current. The permeation route seemed to be localized on hair follicle region. These results suggest that PAMAM dendrimers can permeate into CCP and change the magnitude and direction of EOF. Overall, we obtained a better understanding on the mechanistic insights into the electroosmosis phenomena and its role on flux during iontophoresis.
这项工作的目的是评估聚酰胺 - 胺（PAMAM）树枝状大分子对经皮肤电渗流（EOF）的影响。研究了树枝状大分子的尺寸和浓度的影响，分别使用第1代、第4代和第7代树枝状大分子（分别为G1、G4和G7）。作为EOF方向和大小的标记分子，使用了中性分子对乙酰氨基酚（AAP）。使用G4 - 异硫氰酸荧光素（FITC）偶联物和共聚焦显微镜观察树枝状大分子渗透到皮肤的导电孔（CCP）中的情况。在没有树枝状大分子的情况下，AAP的阳极通量远高于阴极通量或被动通量。当加入G1树枝状大分子时，阳极通量降低，推测是由于G1树枝状大分子与CCP中的净负电荷结合导致EOF降低。随着代数增加，观察到阳极通量有更大的降低，并且EOF的方向发生了反转。用于制备树枝状大分子溶液的少量甲醇也导致了AAP阳极通量的降低。通过共聚焦激光扫描显微镜（CLSM）研究垂直于皮肤表面的横截面视图显示，G4树枝状大分子 - FITC偶联物（G4 - FITC）在阳极电流下可以渗透到活表皮和真皮中。渗透途径似乎定位于毛囊区域。这些结果表明，PAMAM树枝状大分子可以渗透到CCP中并改变EOF的大小和方向。总体而言，我们对电渗现象及其在离子电渗疗法中对通量的作用的机制有了更好的理解。
