Ha Yeonjeong, Kwon Jung-Hwan
Division of Environmental Science and Ecological Engineering, Korea University 145 Anam-ro Seongbuk-gu Seoul 02841 Republic of Korea
RSC Adv. 2020 Jun 10;10(38):22343-22351. doi: 10.1039/d0ra03108a.
Polyhexamethylene guanidine (PHMG) is a cationic antimicrobial oligomer that has been used prevalently over the past few decades. However, due to the lack of inhalation toxicity assessment of PHMG, it has caused severe health damage, including fatal lung fibrosis, after being used as one of the major active ingredients of humidifier disinfectants in Korea. Because the first step of the entry of PHMG into airway is its association with cell membranes, the distribution of PHMG between lipid membranes and water is very important to know the depositional flux in the respiratory systems and related toxic mechanisms. We developed a quantitative method to determine the distribution constant ( ) of PHMG between solid supported lipid membranes and water and evaluated the effects of lipid membrane compositions on the of PHMG. PHMG accumulated into anionic lipid membranes rapidly compared to into cationic or zwitterionic lipid membranes, suggesting fast adsorption of PHMG onto anionic lipid head groups. values with anionic/zwitterionic lipid mixtures were higher than values with anionic lipids only, potentially due to the later phase separation after preferential interaction between PHMG and anionic lipids in lipid mixtures. In addition, values increased with increasing single acyl chain lipid content in unsaturated lipids and decreasing cholesterol content. These results imply that changes in lipid spontaneous curvature and lipid bilayer packing density also affect the membrane distribution of PHMG.
聚六亚甲基胍（PHMG）是一种阳离子抗菌低聚物，在过去几十年中被广泛使用。然而，由于缺乏对PHMG的吸入毒性评估，它在韩国被用作加湿器消毒剂的主要活性成分之一后，造成了严重的健康损害，包括致命的肺纤维化。由于PHMG进入气道的第一步是其与细胞膜的结合，了解PHMG在脂质膜和水之间的分布对于知晓其在呼吸系统中的沉积通量及相关毒性机制非常重要。我们开发了一种定量方法来测定PHMG在固体支持脂质膜和水之间的分配常数（ ），并评估了脂质膜组成对PHMG的 的影响。与阳离子或两性离子脂质膜相比，PHMG更快地积累到阴离子脂质膜中，这表明PHMG能快速吸附到阴离子脂质头部基团上。阴离子/两性离子脂质混合物的 值高于仅含阴离子脂质的 值，这可能是由于脂质混合物中PHMG与阴离子脂质优先相互作用后出现的后期相分离。此外， 值随着不饱和脂质中单酰基链脂质含量的增加和胆固醇含量的降低而增加。这些结果表明脂质自发曲率和脂质双层堆积密度的变化也会影响PHMG的膜分布。
