Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice
Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice
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DOI：
10.1016/j.jconrel.2023.01.012
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发表时间：
2023-01-12
影响因子：
10.8
通讯作者：
Ishida, Tatsuhiro
中科院分区：
文献类型：
--
作者：
Ibrahim, Mohamed;Shimizu, Taro;Ishida, Tatsuhiro
聚乙二醇（PEG），一种聚醚化合物，可以约300 g/mol至约10，000，000 g/mol的分子量获得。在分子量为~ 750至~ 5000的范围内，PEG通常用于生物缀合技术和纳米制剂中，以改善制剂的循环半衰期并增加其稳定性。在化妆品中，较低分子量的PEG化合物（例如PEG 60或PEG 100）被广泛用作乳化剂和皮肤渗透促进剂。PEG聚合物通常被认为是生物惰性和非免疫原性的。然而，最近有报道称，在从未接受过肠外聚乙二醇化制剂治疗的健康个体中检测到高百分比的“预先存在的”抗PEG抗体。据我们所知，我们是第一个试图找到健康个体中预先存在的抗PEG抗体来源的解释。在小鼠研究中，我们证明了两种市售化妆品中存在的局部应用的PEG衍生物可以有效地渗透角质层并到达体循环。PEG衍生物的皮肤渗透在受伤或以其他方式受损的皮肤中进一步增强。每天应用化妆品PEG衍生物引发免疫系统，诱导抗PEG IgM的产生。在具有正常皮肤的小鼠中，在第14天检测到抗PEG IgM，而在具有受损皮肤的小鼠中，早在第7天就检测到抗PEG IgM。此外，在具有预诱导的抗PEG IgM循环水平的小鼠中，局部施用来自化妆品的PEG衍生物似乎与预诱导的抗PEG IgM结合，降低血液水平。目前的结果表明，化妆品中的PEG衍生物可能是健康个体中检测到的“预先存在”抗PEG抗体的重要来源。
Polyethylene glycol (PEG), a polyether compound, is available in molecular weights from -300 g/mol to -10,000,000 g/mol. In the molecular weight range of -750 to -5000, PEG is commonly used in bioconjugation technology and nano-formulations to improve the circulation half-life of the formulations and increase their stability. In cosmetics, lower molecular weight PEG compounds such as PEG 60 or PEG 100 are widely used as emulsifiers and skin penetration enhancers. PEG polymers are generally recognized as biologically inert and nonimmunogenic. However, it is recently reported that the "pre-existing" anti-PEG antibodies have been detected in high percentages of healthy individuals who have never received treatment with parenteral PEGylated formulations. To the best of our knowledge, we are the first to attempt to find an explanation for the source of preexisting anti-PEG antibodies in healthy individuals. In a murine study, we demonstrated that topically applied PEG derivatives, present in two commercially available cosmetic products, could efficiently penetrate the stratum corneum and reach the systemic circulation. The skin penetration of PEG derivatives was further enhanced in injured or otherwise compromised skin. Daily application of cosmetic PEG derivatives primed the immune system, inducing anti-PEG IgM production. Anti-PEG IgM was detected by Day 14 in mice with normal skin, while anti-PEG IgM was detected as early as day 7 in mice with compromised skin. In addition, in mice with preinduced circulating levels of anti-PEG IgM, topically applied PEG derivatives from cosmetic products appeared to bind to the pre-induced anti-PEG IgM, lowering blood levels. Current results indicate that PEG derivatives in cosmetic products may be an important contributor to the source of the "pre-existing" anti-PEG antibodies that have been detected in healthy individuals.